Advertisement

Heat Shock Protein 70 and Molecular Confession During Neurodegeneration

  • Komal Panchal
  • Ajay Kumar
  • Anand K. Tiwari
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 14)

Abstract

Molecular chaperones are the group of proteins that participate in the maintenance of cellular homeostasis by regulating several cellular events and protein homeostasis (proteostasis). It has been shown that failure of protein quality control system, formation of protein aggregates and their ectopic accumulation in the neuronal cells is the common pathological hallmark of most of the neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), prion disease and various forms of spinocerebellar ataxia (SCA) etc. Heat shock protein 70 (Hsp70), an evolutionary conserved protein family has been shown to be a key regulator in several neurodegenerative diseases. Hsp70 shows its strong expression in stress condition and is associated with protein folding, refolding of misfolded protein, transport of proteins to different cellular compartments, cell death and cell cycle regulation etc. Several recent studies have suggested that Hsp70 can be a key molecule to address the major pathologies associated with neurodegenerative diseases. This chapter briefly summarizes the Hsp70 and its possible role during neurodegenerative diseases.

Keywords

Heat Shock Protein 70 (Hsp70) Neurodegenerative diseases Alzheimer’s disease (AD) Parkinson’s disease (PD) 

Abbreviations

17-AAG

17-allylamino-17-demethoxygeldanamycin

17-DMAG

17-(dimethylaminoethylamino)-17- demethoxygeldanamycin

α-Syn

α-synuclein

γPKC

Protein kinase Cγ

42

Amyloid Beta 42

AC

Azure C

AD

Alzheimer’s disease

ADP

Adenosine diphosphate

AIF

Apoptosis inducing factor

ALS

Amyotrophic Lateral Sclerosis

Apaf-1

Apoptotic protease activation factor 1

APP

Amyloid precursor protein

AR

Androgen receptor

Ask1

Apoptosis signal-regulating kinase

ATPase

Adenosine tri phosphatease

Bag-1

Bcl-2-associated athanogene-1

Bap

Benzo(a)pyrene

BiP

Binding immunoglobulin protein

CHIP

Carboxy-terminus of HSC70-interacting protein

CMA

Chaperone mediated autophagy

CNS

Central nervous system

DA

Dopaminergic

E. coli

Escherichia coli

ER

Endoplasmic reticulum

FMRP

Fragile X mental retardation protein

GBA

Glucocerebrosidase

GFP

Green fluorescent protein

GGA

Geranylgeranyl acetone

Grp75

Glucose-regulated protein

HD

Huntington disease

HOP

HSP70 and HSP90 organizing protein

HSC

Heat shock cognate

HSF1

Heat shock transcription factor-1

HSP

Heat shock proteins

Hsp70

Heat shock protein 70

IDE

Insulin degrading enzyme

JNK

c-Jun N-terminal kinase

LBs

Lewy bodies

LRRK2

Leucine-rich repeat kinase 2

MAPK

Mitogen-activated protein kinases

MB

Methylene blue

MY

Myricetin

NBD

Nucleotide binding domain

ND

Neurodegenerative diseases

NEF

Nucleotide exchange factor

NF-ƙB

Nuclear factor-kappaB

NFT

Neurofibrillary tangles

PD

Parkinson’s disease

PDB

Protein data bank

PQC

Protein quality control

PTEN

Phosphatase and tensin homolog

rhHSP70

Recombinant human Hsp70

ROS

Reactive oxygen species

SBD

Substrate binding domain

SBMA

Spinal & Bulbar Muscular Atrophy

SCA

Spinocerebellar ataxia

SOD

Superoxide dismutase

Ubl

Ubiquitin-like protein

UCHL-1

Ubiquitin c-terminal hydrolase-1

UPS

Ubiquitin proteasome system

TGF-β1

Transforming growth factor beta 1

TLR4

Toll-like receptor-4

UMN

Upper motor neurons

LMN

Upper motor neurons

NMJ

Neuromuscular junction

FUS

Fused-in-sarcoma

TDP43

TAR DNA binding protein

Notes

Acknowledgements

The work in our laboratory was supported by grants from Department of Science & Technology (DST), New Delhi, India (SR/FT/LS-1/2010), Gujarat State Biotechnology Mission (GSBTM) (GSBTM/MD/PROJECTS/SSA/456/2010-2011), and Gujarat Council on Science & Technology (GUJCOST) (GUJCOST/MRP/2015-16/2680) Gujarat. The Laser Scanning Confocal Microscope facility supported by Department of Biotechnology, India is duly acknowledged.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Abisambra, J., Jinwal, U. K., Miyata, Y., et al. (2013). Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau. Biological Psychiatry, 74, 367–374.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Adachi, H., Katsuno, M., Minamiyama, M., et al. (2003). Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. The Journal of Neuroscience, 23, 2203–2211.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Adachi, H., Katsuno, M., Minamiyama, M., et al. (2005). Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain, 128, 659–670.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Alexander, G. E. (2004). Biology of Parkinson’s disease: Pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues in Clinical Neuroscience, 6, 259–280.PubMedPubMedCentralGoogle Scholar
  5. Andersen, J. K. (2004). Oxidative stress in neurodegeneration: Cause or consequence? Nature Medicine, 10(Suppl), S18–S25.PubMedPubMedCentralGoogle Scholar
  6. Ardley, H. C., & Robinson, P. A. (2004). The role of ubiquitin-protein ligases in neurodegenerative disease. Neurodegenerative Diseases, 1, 71–87.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Ariga, H., Takahashi-Niki, K., Kato, I., Maita, H., Niki, T., & Iguchi-Ariga, S. M. (2013). Neuroprotective function of DJ-1 in Parkinson’s disease. Oxidative Medicine and Cellular Longevity, 2013, 683920.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Arya, R., Mallik, M., & Lakhotia, S. C. (2007). Heat shock genes – Integrating cell survival and death. Journal of Biosciences, 32, 595–610.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Auluck, P. K., Chan, H. Y., Trojanowski, J. Q., Lee, V. M., & Bonini, N. M. (2002). Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science, 295, 865–868.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bagatell, R., Paine-Murrieta, G. D., Taylor, C. W., Pulcini, E. J., Akinaga, S., Benjamin, I. J., & Whitesell, L. (2000). Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of Hsp90-binding agents. Clinical Cancer Research, 8, 3312–3318.Google Scholar
  11. Bailey, C. K., Andriola, I. F., Kampinga, H. H., & Merry, D. E. (2002). Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Human Molecular Genetics, 11, 515–523.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Ballatore, C., Lee, V. M., & Trojanowski, J. Q. (2007). Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nature Reviews. Neuroscience, 8, 663–672.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Banci, L., Bertini, I., Boca, M., Girotto, S., Martinelli, M., Valentine, J. S., & Vieru, M. (2008). SOD1 and amyotrophic lateral sclerosis: Mutations and oligomerization. PLoS One, 3, e1677.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Batelli, S., Albani, D., Rametta, R., Polito, L., Prato, F., Pesaresi, M., Negro, A., & Forloni, G. (2008). DJ-1 modulates alpha-synuclein aggregation state in a cellular model of oxidative stress: Relevance for Parkinson’s disease and involvement of HSP70. PLoS One, 3, e1884.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Beere, H. M. (2001). Stressed to death: Regulation of apoptotic signaling pathways by the heat shock proteins. Science’s STKE, 2001, re1.CrossRefGoogle Scholar
  16. Beyer, K., Domingo-Sabat, M., & Ariza, A. (2009). Molecular pathology of Lewy body diseases. International Journal of Molecular Sciences, 10, 724–745.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Blair, L. J., Sabbagh, J. J., & Dickey, C. A. (2014). Targeting Hsp90 and its co-chaperones to treat Alzheimer’s disease. Expert Opinion on Therapeutic Targets, 18, 1219–1232.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bobkova, N. V., Evgen’ev, M., Garbuz, D. G., et al. (2015). Exogenous Hsp70 delays senescence and improves cognitive function in aging mice. Proceedings of the National Academy of Sciences of the United States of America, 112, 16006–16011.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bonini, N. M., & Gitler, A. D. (2011). Model organisms reveal insight into human neurodegenerative disease: Ataxin-2 intermediate-length polyglutamine expansions are a risk factor for ALS. Journal of Molecular Neuroscience, 45, 676–683.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Broadley, S. A., & Hartl, F. U. (2009). The role of molecular chaperones in human misfolding diseases. FEBS Letters, 583, 2647–2653.PubMedCrossRefGoogle Scholar
  21. Brocchieri, L., Conway de Macario, E., & Macario, A. J. (2008). Hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions. BMC Evolutionary Biology, 8, 19.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Buchman, A. S., Leurgans, S. E., Nag, S., Bennett, D. A., & Schneider, J. A. (2011). Cerebrovascular disease pathology and parkinsonian signs in old age. Stroke, 42, 3183–3189.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Bunton-Stasyshyn, R. K., Saccon, R. A., Fratta, P., & Fisher, E. M. (2015). SOD1 function and its implications for amyotrophic lateral sclerosis pathology: New and renascent themes. The Neuroscientist, 21, 519–529.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Burchell, V. S., Nelson, D. E., Sanchez-Martinez, A., et al. (2013). The Parkinson’s disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nature Neuroscience, 16, 1257–1265.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Carmine-Simmen, K., Proctor, T., Tschape, J., Poeck, B., Triphan, T., Strauss, R., & Kretzschmar, D. (2009). Neurotoxic effects induced by the Drosophila amyloid-beta peptide suggest a conserved toxic function. Neurobiology of Disease, 33, 274–281.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Cassar, M., & Kretzschmar, D. (2016). Analysis of amyloid precursor protein function in Drosophila melanogaster. Frontiers in Molecular Neuroscience, 9, 61.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Chakraborty, R., Vepuri, V., Mhatre, S. D., et al. (2011). Characterization of a Drosophila Alzheimer’s disease model: Pharmacological rescue of cognitive defects. PLoS One, 6, e20799.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Cookson, M. R. (2012). Evolution of neurodegeneration. Current Biology, 22, R753–R761.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Cummings, C. J., Sun, Y., Opal, P., Antalffy, B., Mestril, R., Orr, H. T., Dillmann, W. H., & Zoghbi, H. Y. (2001). Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Human Molecular Genetics, 10, 1511–1518.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Dachsel, J. C., Wider, C., Vilarino-Guell, C., et al. (2011). Death-associated protein kinase 1 variation and Parkinson’s disease. European Journal of Neurology, 18, 1090–1093.PubMedCrossRefGoogle Scholar
  31. Daugaard, M., Rohde, M., & Jaattela, M. (2007). The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Letters, 581, 3702–3710.CrossRefPubMedGoogle Scholar
  32. de Diego-Otero, Y., Romero-Zerbo, Y., el Bekay, R., Decara, J., Sanchez, L., Rodriguez-de Fonseca, F., & del Arco-Herrera, I. (2009). Alpha-tocopherol protects against oxidative stress in the fragile X knockout mouse: An experimental therapeutic approach for the Fmr1 deficiency. Neuropsychopharmacology, 34, 1011–1026.PubMedCrossRefPubMedCentralGoogle Scholar
  33. de Tullio, M. B., Morelli, L., & Castano, E. M. (2008). The irreversible binding of amyloid peptide substrates to insulin-degrading enzyme: A biological perspective. Prion, 2, 51–56.PubMedPubMedCentralCrossRefGoogle Scholar
  34. de Tullio, M. B., Castelletto, V., Hamley, I. W., Martino Adami, P. V., Morelli, L., & Castano, E. M. (2013). Proteolytically inactive insulin-degrading enzyme inhibits amyloid formation yielding non-neurotoxic abeta peptide aggregates. PLoS One, 8, e59113.PubMedPubMedCentralCrossRefGoogle Scholar
  35. DeMaagd, G., & Philip, A. (2015). Parkinson’s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P T, 40, 504–532.PubMedPubMedCentralGoogle Scholar
  36. Ding, X., & Goldberg, M. S. (2009). Regulation of LRRK2 stability by the E3 ubiquitin ligase CHIP. PLoS One, 4, e5949.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Donnelly, B. F., Needham, P. G., Snyder, A. C., Roy, A., Khadem, S., Brodsky, J. L., & Subramanya, A. R. (2013). Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis. The Journal of Biological Chemistry, 288, 13124–13135.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Dou, F., Netzer, W. J., Tanemura, K., Li, F., Hartl, F. U., Takashima, A., Gouras, G. K., Greengard, P., & Xu, H. (2003). Chaperones increase association of tau protein with microtubules. Proceedings of the National Academy of Sciences of the United States of America, 100, 721–726.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Ebrahimi-Fakhari, D., Saidi, L. J., & Wahlster, L. (2013). Molecular chaperones and protein folding as therapeutic targets in Parkinson’s disease and other synucleinopathies. Acta Neuropathologica Communications, 1, 79.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Elefant, F., & Palter, K. B. (1999). Tissue-specific expression of dominant negative mutant Drosophila HSC70 causes developmental defects and lethality. Molecular Biology of the Cell, 10, 2101–2117.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Evans, C. G., Wisen, S., & Gestwicki, J. E. (2006). Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. The Journal of Biological Chemistry, 281, 33182–33191.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Feany, M. B., & Bender, W. W. (2000). A Drosophila model of Parkinson’s disease. Nature, 404, 394–398.PubMedCrossRefPubMedCentralGoogle Scholar
  43. Fernandez-Funez, P., Sanchez-Garcia, J., de Mena, L., Zhang, Y., Levites, Y., Khare, S., Golde, T. E., & Rincon-Limas, D. E. (2016). Holdase activity of secreted Hsp70 masks amyloid-beta42 neurotoxicity in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 113, E5212–E5221.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Flaherty, K. M., DeLuca-Flaherty, C., & McKay, D. B. (1990). Three-dimensional structure of the ATPase fragment of a 70K heat-shock cognate protein. Nature, 346, 623–628.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Gething, M.-J., & Sambrook, J. (1992). Protein folding in the cell. Nature, 355, 33–45.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Gidalevitz, T., Prahlad, V., & Morimoto, R. I. (2011). The stress of protein misfolding: From single cells to multicellular organisms. Cold Spring Harbor Perspectives in Biology, 3, a009704.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Gifondorwa, D. J., Robinson, M. B., Hayes, C. D., Taylor, A. R., Prevette, D. M., Oppenheim, R. W., Caress, J., & Milligan, C. E. (2007). Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. The Journal of Neuroscience, 27, 13173–13180.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Giraldez-Perez, R., Antolin-Vallespin, M., Munoz, M., & Sanchez-Capelo, A. (2014). Models of alpha-synuclein aggregation in Parkinson’s disease. Acta Neuropathologica Communications, 2, 176.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Glenner, G. G., & Wong, C. W. (1984). Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochemical and Biophysical Research Communications, 120, 885–890.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Goedert, M., Jakes, R., & Spillantini, M. G. (2017). The synucleinopathies: Twenty years on. Journal of Parkinsons disease, 7, S53–S71.Google Scholar
  51. Gold, B. G. (1997). FK506 and the role of immunophilins in nerve regeneration. Molecular Neurobiology, 15, 285–306.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Gong, C. X., & Iqbal, K. (2008). Hyperphosphorylation of microtubule-associated protein tau: A promising therapeutic target for Alzheimer disease. Current Medicinal Chemistry, 15, 2321–2328.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Gordon, P. H. (2013). Amyotrophic Lateral Sclerosis: An update for 2013 clinical features, pathophysiology, management and therapeutic trials. Aging and Disease, 4, 295–310.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Grunseich, C., Rinaldi, C., & Fischbeck, K. H. (2014). Spinal and bulbar muscular atrophy: Pathogenesis and clinical management. Oral Diseases, 20, 6–9.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Gupta, R. S., & Singh, B. (1994). Phylogenetic analysis of 70 kD heat shock protein sequences suggests a chimeric origin for the eukaryotic cell nucleus. Current Biology, 4, 1104–1114.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Hansson, O., Nylandsted, J., Castilho, R. F., Leist, M., Jaattela, M., & Brundin, P. (2003). Overexpression of heat shock protein 70 in R6/2 Huntington’s disease mice has only modest effects on disease progression. Brain Research, 970, 47–57.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Hartl, F. U. (1996). Molecular chaperones in cellular protein folding. Nature, 381, 571–579.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Hay, D. G., Sathasivam, K., Tobaben, S., et al. (2004). Progressive decrease in chaperone protein levels in a mouse model of Huntington’s disease and induction of stress proteins as a therapeutic approach. Human Molecular Genetics, 13, 1389–1405.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Helmlinger, D., Hardy, S., Sasorith, S., et al. (2004). Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes. Human Molecular Genetics, 13, 1257–1265.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Hendrick, J. P., & Hartl, F.-U. (1993). Molecular chaperone functions of heat-shock proteins. Annual Review of Biochemistry, 62, 349–384.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Huang, W. J., Zhang, X., & Chen, W. W. (2016). Role of oxidative stress in Alzheimer’s disease. Biomed Rep, 4, 519–522.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Hunt, C., & Morimoto, R. I. (1985). Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proceedings of the National Academy of Sciences of the United States of America, 82, 6455–6459.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Iijima, K., Chiang, H. C., Hearn, S. A., et al. (2008). Abeta42 mutants with different aggregation profiles induce distinct pathologies in Drosophila. PLoS One, 3, e1703.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Iijima-Ando, K., & Iijima, K. (2010). Transgenic Drosophila models of Alzheimer’s disease and tauopathies. Brain Structure & Function, 214, 245–262.CrossRefGoogle Scholar
  65. Iqbal, K., Liu, F., Gong, C. X., Alonso Adel, C., & Grundke-Iqbal, I. (2009). Mechanisms of tau-induced neurodegeneration. Acta Neuropathologica, 118, 53–69.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Jaattela, M., & Wissing, D. (1992). Emerging role of heat shock proteins in biology and medicine. Annals of Medicine, 24, 249–258.PubMedCrossRefPubMedCentralGoogle Scholar
  67. Jahn, H. (2013). Memory loss in Alzheimer’s disease. Dialogues in Clinical Neuroscience, 15, 445.PubMedPubMedCentralGoogle Scholar
  68. Jain, M. R., Ge, W. W., Elkabes, S., & Li, H. (2008). Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by proteomic studies of animal models. Proteomics. Clinical Applications, 2, 670–684.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Jana, N. R., Dikshit, P., Goswami, A., Kotliarova, S., Murata, S., Tanaka, K., & Nukina, N. (2005). Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. The Journal of Biological Chemistry, 280, 11635–11640.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Jin, P., Zarnescu, D. C., Zhang, F., Pearson, C. E., Lucchesi, J. C., Moses, K., & Warren, S. T. (2003). RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. Neuron, 39, 739–747.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Jinwal, U. K., Miyata, Y., Koren, J., 3rd, et al. (2009). Chemical manipulation of hsp70 ATPase activity regulates tau stability. The Journal of Neuroscience, 29, 12079–12088.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Kakimura, J., Kitamura, Y., Takata, K., et al. (2002). Microglial activation and amyloid-beta clearance induced by exogenous heat-shock proteins. The FASEB Journal, 16, 601–603.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Kakkar, V., Kuiper, E. F., Pandey, A., Braakman, I., & Kampinga, H. H. (2016). Versatile members of the DNAJ family show Hsp70 dependent anti-aggregation activity on RING1 mutant parkin C289G. Scientific Reports, 6, 34830.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Kalia, L. V., Kalia, S. K., & Lang, A. E. (2015). Disease-modifying strategies for Parkinson’s disease. Movement Disorders, 30, 1442–1450.PubMedCrossRefPubMedCentralGoogle Scholar
  75. Kampinga, H. H., & Bergink, S. (2016). Heat shock proteins as potential targets for protective strategies in neurodegeneration. Lancet Neurology, 15, 748–759.PubMedCrossRefPubMedCentralGoogle Scholar
  76. Katsuno, M., Sang, C., Adachi, H., Minamiyama, M., Waza, M., Tanaka, F., Doyu, M., & Sobue, G. (2005). Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. Proceedings of the National Academy of Sciences of the United States of America, 102, 16801–16806.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Kennedy, W. R., & Alter, M. (2000). Progressive proximal spinal and bulbar muscular atrophy of late onset: A sex-linked recessive trait. Journal of Clinical Neuromuscular Disease, 2, 3–5.PubMedCrossRefPubMedCentralGoogle Scholar
  78. Kennedy, W. R., Alter, M., & Sung, J. H. (1968). Progressive proximal spinal and bulbar muscular atrophy of late onset: A sex-linked recessive trait. Neurology, 18, 671–671.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Kikis, E. A. (2016). The struggle by Caenorhabditis elegans to maintain proteostasis during aging and disease. Biology Direct, 11, 58.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Klein, C., & Westenberger, A. (2012). Genetics of Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine, 2, a008888.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Klucken, J., Shin, Y., Masliah, E., Hyman, B. T., & McLean, P. J. (2004). Hsp70 reduces alpha-synuclein aggregation and toxicity. The Journal of Biological Chemistry, 279, 25497–25502.PubMedCrossRefPubMedCentralGoogle Scholar
  82. Ko, H. S., Bailey, R., Smith, W. W., et al. (2009). CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proceedings of the National Academy of Sciences of the United States of America, 106, 2897–2902.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Kobayashi, Y., Kume, A., Li, M., Doyu, M., Hata, M., Ohtsuka, K., & Sobue, G. (2000). Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. The Journal of Biological Chemistry, 275, 8772–8778.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Koren, J., 3rd, Jinwal, U. K., Lee, D. C., Jones, J. R., Shults, C. L., Johnson, A. G., Anderson, L. J., & Dickey, C. A. (2009). Chaperone signalling complexes in Alzheimer’s disease. Journal of Cellular and Molecular Medicine, 13, 619–630.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Kumar, A., & Tiwari, A. K. (2017). Molecular chaperone Hsp70 and its constitutively active form Hsc70 play an indispensable role during eye development of Drosophila melanogaster. Molecular Neurobiology, 55, 4345–4361.Google Scholar
  86. Kumar, P., Pradhan, K., Karunya, R., Ambasta, R. K., & Querfurth, H. W. (2012). Cross-functional E3 ligases Parkin and C-terminus Hsp70-interacting protein in neurodegenerative disorders. Journal of Neurochemistry, 120, 350–370.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Kumar, A., Christian, P. K., Panchal, K., Guruprasad, B. R., & Tiwari, A. K. (2017). Supplementation of spirulina (Arthrospira platensis) improves lifespan and locomotor activity in paraquat-sensitive DJ-1β Δ93 Flies, a Parkinson’s disease model in Drosophila melanogaster. Journal of Dietary Supplements, 14, 573–588.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Kityk, R., Kopp, J., Sinning, I., & Mayer, M. P. (2012). Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones. Molecular Cell, 48, 863–874.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Krench, M., & Littleton, J. T. (2013). Modeling Huntington disease in Drosophila: Insights into axonal transport defects and modifiers of toxicity. Fly (Austin), 7, 229–236.CrossRefGoogle Scholar
  90. La Spada, A. (2014). Spinal and bulbar muscular atrophy.Google Scholar
  91. Labrador-Garrido, A., Bertoncini, C. W., & Roodveldt, C. (2011). The HSP70 chaperone system in Parkinson’s disease. In: Etiology and pathophysiology of Parkinson’s disease. InTech.Google Scholar
  92. Laffita-Mesa, J. M., Rodriguez Pupo, J. M., Moreno Sera, R., et al. (2013). De novo mutations in ataxin-2 gene and ALS risk. PLoS One, 8, s.CrossRefGoogle Scholar
  93. Leak, R. K. (2014). Heat shock proteins in neurodegenerative disorders and aging. J Cell Commun Signal, 8, 293–310.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Lev, N., Roncevic, D., Ickowicz, D., Melamed, E., & Offen, D. (2006). Role of DJ-1 in Parkinson’s disease. Journal of Molecular Neuroscience, 29, 215–225.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Lewis, E. A., & Smith, G. A. (2016). Using Drosophila models of Huntington’s disease as a translatable tool. Journal of Neuroscience Methods, 265, 89–98.PubMedCrossRefPubMedCentralGoogle Scholar
  96. Li, C. Y., Lee, J. S., Ko, Y. G., Kim, J. I., & Seo, J. S. (2000). Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation. The Journal of Biological Chemistry, 275, 25665–25671.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Li, H., Liu, L., Xing, D., & Chen, W. R. (2010). Inhibition of the JNK/Bim pathway by Hsp70 prevents Bax activation in UV-induced apoptosis. FEBS Letters, 584, 4672–4678.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Li, J.-Q., Tan, L., & Yu, J.-T. (2014). The role of the LRRK2 gene in Parkinsonism. Molecular Neurodegeneration, 9, 47.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Lindquist, S., & Craig, E. A. (1988). The heat-shock proteins. Annual Review of Genetics, 22, 631–677.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Liu, J., Shinobu, L. A., Ward, C. M., Young, D., & Cleveland, D. W. (2005). Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis. Journal of Neurochemistry, 93, 875–882.PubMedCrossRefPubMedCentralGoogle Scholar
  101. Lu, B., & Vogel, H. (2009). Drosophila models of neurodegenerative diseases. Annual Review of Pathology, 4, 315–342.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Lu, R. C., Tan, M. S., Wang, H., Xie, A. M., Yu, J. T., & Tan, L. (2014). Heat shock protein 70 in Alzheimer’s disease. BioMed Research International, 2014, 435203.PubMedPubMedCentralGoogle Scholar
  103. Ludolph, A., Drory, V., Hardiman, O., Nakano, I., Ravits, J., Robberecht, W., & Shefner, J. (2015). A revision of the El Escorial criteria - 2015. Amyotroph Lateral Scler Frontotemporal Degener, 16, 291–292.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Luo, X., Zuo, X., Zhou, Y., Zhang, B., Shi, Y., Liu, M., Wang, K., McMillian, D. R., & Xiao, X. (2008). Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytes. Arthritis Research & Therapy, 10, R41.CrossRefGoogle Scholar
  105. Mackenzie, I. R. A., & Rademakers, R. (2008). The role of TDP-43 in amyotrophic lateral sclerosis and frontotemporal dementia. Current Opinion in Neurology, 21, 693.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Magrinelli, F., Picelli, A., Tocco, P., Federico, A., Roncari, L., Smania, N., Zanette, G., & Tamburin, S. (2016). Pathophysiology of motor dysfunction in Parkinson’s disease as the rationale for drug treatment and rehabilitation. Parkinsons Disease, 2016, 9832839.Google Scholar
  107. Malik, B., Nirmalananthan, N., Gray, A. L., La Spada, A. R., Hanna, M. G., & Greensmith, L. (2013). Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: Implications for therapy. Brain, 136, 926–943.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Maraganore, D. M., Lesnick, T. G., Elbaz, A., et al. (2004). UCHL1 is a Parkinson’s disease susceptibility gene. Annals of Neurology, 55, 512–521.PubMedCrossRefPubMedCentralGoogle Scholar
  109. Marti, M. J., Tolosa, E., & Campdelacreu, J. (2003). Clinical overview of the synucleinopathies. Movement Disorders, 18, 21–27.CrossRefGoogle Scholar
  110. Martin, L. J. (2001). Neuronal cell death in nervous system development, disease, and injury (Review). International Journal of Molecular Medicine, 7, 455–478.PubMedGoogle Scholar
  111. Meijering, R. A., Henning, R. H., & Brundel, B. J. (2014). Reviving the protein quality control system: Therapeutic target for cardiac disease in the elderly. Trends in Cardiovascular Medicine, 25, 243–247.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Miyata, Y., Koren, J., Kiray, J., Dickey, C. A., & Gestwicki, J. E. (2011). Molecular chaperones and regulation of tau quality control: Strategies for drug discovery in tauopathies. Future Medicinal Chemistry, 3, 1523–1537.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Miyazaki, D., Nakamura, A., Hineno, A., Kobayashi, C., Kinoshita, T., Yoshida, K., & Ikeda, S. (2016). Elevation of serum heat-shock protein levels in amyotrophic lateral sclerosis. Neurological Sciences, 37, 1277–1281.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Moloney, A., Sattelle, D. B., Lomas, D. A., & Crowther, D. C. (2010). Alzheimer’s disease: Insights from Drosophila melanogaster models. Trends in Biochemical Sciences, 35, 228–235.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Moore, D. J., West, A. B., Dikeman, D. A., Dawson, V. L., & Dawson, T. M. (2008). Parkin mediates the degradation-independent ubiquitination of Hsp70. Journal of Neurochemistry, 105, 1806–1819.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Morais, V. A., Verstreken, P., Roethig, A., et al. (2009). Parkinson’s disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Molecular Medicine, 1, 99–111.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Moreira, P. I., Carvalho, C., Zhu, X., Smith, M. A., & Perry, G. (2010). Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. Biochimica et Biophysica Acta, 1802, 2–10.PubMedCrossRefPubMedCentralGoogle Scholar
  118. Morozov, A. V., Astakhova, T. M., Garbuz, D. G., Krasnov, G. S., Bobkova, N. V., Zatsepina, O. G., Karpov, V. L., & Evgen’ev, M. B. (2017). Interplay between recombinant Hsp70 and proteasomes: Proteasome activity modulation and ubiquitin-independent cleavage of Hsp70. Cell Stress & Chaperones, 22(5), 687.CrossRefGoogle Scholar
  119. Mosser, D. D., Caron, A. W., Bourget, L., Meriin, A. B., Sherman, M. Y., Morimoto, R. I., & Massie, B. (2000). The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Molecular and Cellular Biology, 20, 7146–7159.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Muchowski, P. J., Schaffar, G., Sittler, A., Wanker, E. E., Hayer-Hartl, M. K., & Hartl, F. U. (2000). Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proceedings of the National Academy of Sciences of the United States of America, 97, 7841–7846.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Munoz-Soriano, V., & Paricio, N. (2011). Drosophila models of Parkinson’s disease: Discovering relevant pathways and novel therapeutic strategies. Parkinsons Dis, 2011, 520640.PubMedPubMedCentralGoogle Scholar
  122. Najarzadegan, M. R., Ataei, E., & Akbarzadeh, F. (2016). The role of heat shock proteins in Alzheimer disease: A systematic review. J Syndromes, 3, 6.Google Scholar
  123. Neckers, L., & Workman, P. (2012). Hsp90 molecular chaperone inhibitors: Are we there yet? Clinical Cancer Research, 1, 64–76.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Neef, D. W., Jaeger, A. M., & Thiele, D. J. (2011). Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nature Reviews. Drug Discovery, 10, 930–944.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Niizuma, K., Endo, H., & Chan, P. H. (2009). Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. Journal of Neurochemistry, 109(Suppl 1), 133–138.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Nolan, M., Talbot, K., & Ansorge, O. (2016). Pathogenesis of FUS-associated ALS and FTD: Insights from rodent models. Acta Neuropathologica Communications, 4, 99.PubMedPubMedCentralCrossRefGoogle Scholar
  127. O’Donnell, W. T., & Warren, S. T. (2002). A decade of molecular studies of fragile X syndrome. Annual Review of Neuroscience, 25, 315–338.PubMedCrossRefPubMedCentralGoogle Scholar
  128. Ogawa, K., Seki, T., Onji, T., Adachi, N., Tanaka, S., Hide, I., Saito, N., & Sakai, N. (2013). Mutant gammaPKC that causes spinocerebellar ataxia type 14 upregulates Hsp70, which protects cells from the mutant’s cytotoxicity. Biochemical and Biophysical Research Communications, 440, 25–30.PubMedCrossRefPubMedCentralGoogle Scholar
  129. Oh, S. Y., He, F., Krans, A., Frazer, M., Taylor, J. P., Paulson, H. L., & Todd, P. K. (2015). RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome. Human Molecular Genetics, 24, 4317–4326.PubMedPubMedCentralCrossRefGoogle Scholar
  130. Orr, H. T., & Zoghbi, H. Y. (2007). Trinucleotide repeat disorders. Annual Review of Neuroscience, 30, 575–621.PubMedCrossRefPubMedCentralGoogle Scholar
  131. Ou, J. R., Tan, M. S., Xie, A. M., Yu, J. T., & Tan, L. (2014). Heat shock protein 90 in Alzheimer’s disease. BioMed Research International, 2014, 796869.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Ousman, S. S., Frederick, A., & Lim, E. F. (2017). Chaperone proteins in the central nervous system and peripheral nervous system after nerve injury. Frontiers in Neuroscience, 11, 79.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Paul, S., & Mahanta, S. (2014). Association of heat-shock proteins in various neurodegenerative disorders: Is it a master key to open the therapeutic door? Molecular and Cellular Biochemistry, 386, 45–61.PubMedCrossRefPubMedCentralGoogle Scholar
  134. Paulson, H. L. (2009). The spinocerebellar ataxias. Journal of neuro-ophthalmology: The official journal of the North American Neuro-Ophthalmology Society, 29, 227.CrossRefGoogle Scholar
  135. Phukan, J. (2010). Arimoclomol, a coinducer of heat shock proteins for the potential treatment of amyotrophic lateral sclerosis. IDrugs, 13, 482–496.PubMedGoogle Scholar
  136. Pickrell, A. M., & Youle, R. J. (2015). The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron, 85, 257–273.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Pockley, A. G. (2001). Heat shock proteins in health and disease: Therapeutic targets or therapeutic agents? Expert Reviews in Molecular Medicine, 3, 1–21.PubMedCrossRefPubMedCentralGoogle Scholar
  138. Pooler, A. M., Phillips, E. C., Lau, D. H., Noble, W., & Hanger, D. P. (2013). Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Reports, 14, 389–394.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Prussing, K., Voigt, A., & Schulz, J. B. (2013). Drosophila melanogaster as a model organism for Alzheimer’s disease. Molecular Neurodegeneration, 8, 35.PubMedPubMedCentralCrossRefGoogle Scholar
  140. Rademakers, R., Stewart, H., Dejesus-Hernandez, M., et al. (2010). Fus gene mutations in familial and sporadic amyotrophic lateral sclerosis. Muscle & Nerve, 42, 170–176.CrossRefGoogle Scholar
  141. Ravagnan, L., Gurbuxani, S., Susin, S. A., et al. (2001). Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nature Cell Biology, 3, 839–843.CrossRefPubMedGoogle Scholar
  142. Repalli, J., & Meruelo, D. (2015). Screening strategies to identify HSP70 modulators to treat Alzheimer’s disease. Drug Design, Development and Therapy, 9, 321–331.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Ritossa, F. M. (1964). Experimental activation of specific loci in polytene chromosomes of Drosophila. Experimental Cell Research, 35, 601–607.PubMedCrossRefGoogle Scholar
  144. Roodveldt, C., Bertoncini, C. W., Andersson, A., et al. (2009). Chaperone proteostasis in Parkinson’s disease: Stabilization of the Hsp70/α-synuclein complex by Hip. The EMBO Journal, 28, 3758–3770.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Ross, C. A., & Poirier, M. A. (2004). Protein aggregation and neurodegenerative disease. Nature Medicine, 10(Suppl), S10–S17.PubMedCrossRefGoogle Scholar
  146. Rubin, D. M., Mehta, A. D., Zhu, J., Shoham, S., Chen, X., Wells, Q. R., & Palter, K. B. (1993). Genomic structure and sequence analysis of Drosophila melanogaster HSC70 genes. Gene, 128, 155–163.PubMedCrossRefGoogle Scholar
  147. Sabirzhanov, B., Stoica, B. A., Hanscom, M., Piao, C. S., & Faden, A. I. (2012a). Over-expression of HSP70 attenuates caspase-dependent and caspase-independent pathways and inhibits neuronal apoptosis. Journal of Neurochemistry, 123, 542–554.PubMedPubMedCentralCrossRefGoogle Scholar
  148. Sabirzhanov, B., Stoica, B. A., Hanscom, M., Piao, C. S., & Faden, A. I. (2012b). Over-expression of HSP70 attenuates caspase-dependent and caspase-independent pathways and inhibits neuronal apoptosis. Journal of Neurochemistry, 123, 542–554.PubMedPubMedCentralCrossRefGoogle Scholar
  149. Saleh, A., Srinivasula, S. M., Balkir, L., Robbins, P. D., & Alnemri, E. S. (2000). Negative regulation of the Apaf-1 apoptosome by Hsp70. Nature Cell Biology, 2, 476–483.CrossRefPubMedGoogle Scholar
  150. Sau, D., De Biasi, S., Vitellaro-Zuccarello, L., et al. (2007). Mutation of SOD1 in ALS: A gain of a loss of function. Human Molecular Genetics, 16, 1604–1618.PubMedCrossRefGoogle Scholar
  151. Schaffar, G., Breuer, P., Boteva, R., et al. (2004). Cellular toxicity of polyglutamine expansion proteins: Mechanism of transcription factor deactivation. Molecular Cell, 15, 95–105.PubMedCrossRefGoogle Scholar
  152. Scotter, E. L., Chen, H. J., & Shaw, C. E. (2015). TDP-43 proteinopathy and ALS: Insights into disease mechanisms and therapeutic targets. Neurotherapeutics, 12, 352–363.PubMedPubMedCentralCrossRefGoogle Scholar
  153. Shaaban, K. A., Wang, X., Elshahawi, S. I., et al. (2013). Herbimycins D-F, ansamycin analogues from Streptomyces sp. RM-7-15. Journal of Natural Products, 76, 1619–1626.PubMedCrossRefGoogle Scholar
  154. Sharma, A., Lyashchenko, A. K., Lu, L., et al. (2016). ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function. Nature Communications, 7, 10465.PubMedPubMedCentralCrossRefGoogle Scholar
  155. Sheikh, S., Safia, H.,. E., & Mir, S. S. (2013). Neurodegenerative diseases: Multifactorial conformational diseases and their rherapeutic interventions. Journal Neurodegenerative Disease, 2013, 563481.CrossRefGoogle Scholar
  156. Shimura, H., Schwartz, D., Gygi, S. P., & Kosik, K. S. (2004). CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. The Journal of Biological Chemistry, 279, 4869–4876.PubMedCrossRefGoogle Scholar
  157. Shin, Y., Klucken, J., Patterson, C., Hyman, B. T., & McLean, P. J. (2005). The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways. The Journal of Biological Chemistry, 280, 23727–23734.PubMedCrossRefGoogle Scholar
  158. Shopland, L. S., & Lis, J. T. (1996). HSF recruitment and loss at most Drosophila heat shock loci is coordinated and depends on proximal promoter sequences. Chromosoma, 105, 158–171.PubMedCrossRefGoogle Scholar
  159. Shukla, A. K., Pragya, P., Chaouhan, H. S., Tiwari, A. K., Patel, D. K., Abdin, M. Z., & Chowdhuri, D. K. (2014). Heat shock protein-70 (Hsp-70) suppresses paraquat-induced neurodegeneration by inhibiting JNK and caspase-3 activation in drosophila model of Parkinson’s disease. PLoS One, 9, 98886.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Silva, A. R., Santos, A. C., Farfel, J. M., et al. (2014). Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer’s disease. PLoS One, 9, e99897.PubMedPubMedCentralCrossRefGoogle Scholar
  161. Singh, R. P., Sharad, S., & Kapur, S. (2004). Free radicals and oxidative stress in neurodegenerative diseases: Relevance of dietary antioxidants. Journal Indian Academy Clinical Medicine, 5, 218–225.Google Scholar
  162. Sittler, A., Lurz, R., Lueder, G., Priller, J., Lehrach, H., Hayer-Hartl, M. K., Hartl, F. U., & Wanker, E. E. (2001). Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Human Molecular Genetics, 10, 1307–1315.PubMedCrossRefGoogle Scholar
  163. Slow, E. J., Graham, R. K., Osmand, A. P., et al. (2005). Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proceedings of the National Academy of Sciences of the United States of America, 102, 11402–11407.PubMedPubMedCentralCrossRefGoogle Scholar
  164. Soga, S., Akinaga, S., & Shiotsu, Y. (2013). Hsp90 inhibitors as anti-cancer agents, from basic discoveries to clinical development. Current Pharmaceutical Design, 3, 366–376.PubMedCrossRefPubMedCentralGoogle Scholar
  165. Soto, C., & Estrada, L. D. (2008). Protein misfolding and neurodegeneration. Archives of Neurology, 65, 184–189.PubMedCrossRefGoogle Scholar
  166. Stankiewicz, A. R., Lachapelle, G., Foo, C. P., Radicioni, S. M., & Mosser, D. D. (2005). Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. The Journal of Biological Chemistry, 280, 38729–38739.PubMedCrossRefGoogle Scholar
  167. Starkov, A. A., & Beal, F. M. (2008). Portal to Alzheimer’s disease. Nature Medicine, 14, 1020–1021.PubMedPubMedCentralCrossRefGoogle Scholar
  168. Stefanis, L. (2012). Alpha-synuclein in Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine, 2, a009399.PubMedPubMedCentralCrossRefGoogle Scholar
  169. Tagawa, K., Marubuchi, S., Qi, M. L., et al. (2007). The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. The Journal of Neuroscience, 27, 868–880.PubMedCrossRefPubMedCentralGoogle Scholar
  170. Taroni, F., & DiDonato, S. (2004). Pathways to motor incoordination: The inherited ataxias. Nature Reviews. Neuroscience, 5, 641–655.PubMedCrossRefPubMedCentralGoogle Scholar
  171. Tichauer, J. E., Flores, B., Soler, B., Eugenin-von Bernhardi, L., Ramirez, G., & von Bernhardi, R. (2014). Age-dependent changes on TGFbeta1 Smad3 pathway modify the pattern of microglial cell activation. Brain, Behavior, and Immunity, 37, 187–196.PubMedCrossRefPubMedCentralGoogle Scholar
  172. Tofaris, G. K., Razzaq, A., Ghetti, B., Lilley, K. S., & Spillantini, M. G. (2003). Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function. The Journal of Biological Chemistry, 278, 44405–44411.PubMedCrossRefPubMedCentralGoogle Scholar
  173. Tsai, H. F., Lin, S. J., Li, C., & Hsieh, M. (2005). Decreased expression of Hsp27 and Hsp70 in transformed lymphoblastoid cells from patients with spinocerebellar ataxia type 7. Biochemical and Biophysical Research Communications, 334, 1279–1286.PubMedCrossRefPubMedCentralGoogle Scholar
  174. Turturici, G., Sconzo, G., & Geraci, F. (2011). Hsp70 and its molecular role in nervous system diseases. Biochemistry Research International, 2011, 618127.PubMedPubMedCentralCrossRefGoogle Scholar
  175. Upadhaya, A. R., Lungrin, I., Yamaguchi, H., Fandrich, M., & Thal, D. R. (2012). High-molecular weight Abeta oligomers and protofibrils are the predominant Abeta species in the native soluble protein fraction of the AD brain. Journal of Cellular and Molecular Medicine, 16, 287–295.PubMedPubMedCentralCrossRefGoogle Scholar
  176. Uttara, B., Singh, A. V., Zamboni, P., & Mahajan, R. T. (2009). Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Current Neuropharmacology, 7, 65–74.PubMedPubMedCentralCrossRefGoogle Scholar
  177. Van Drie, J. H. (2011). Protein folding, protein homeostasis, and cancer. Chinese Journal of Cancer, 30, 124–137.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Verghese, J., Abrams, J., Wang, Y., & Morano, K. A. (2012). Biology of the heat shock response and protein chaperones: Budding yeast (Saccharomyces cerevisiae) as a model system. Microbiology and Molecular Biology Reviews, 76, 115–158.PubMedPubMedCentralCrossRefGoogle Scholar
  179. Vigh, L., Literati, P. N., Horvath, I., et al. (1997). Bimoclomol: A nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nature Medicine, 3, 1150–1154.PubMedCrossRefGoogle Scholar
  180. Vogel, M., Mayer, M. P., & Bukau, B. (2006). Allosteric regulation of Hsp70 chaperones involves a conserved interdomain linker. The Journal of Biological Chemistry, 281, 38705–38711.PubMedCrossRefGoogle Scholar
  181. Wacker, J. L., Zareie, M. H., Fong, H., Sarikaya, M., & Muchowski, P. J. (2004). Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nature Structural & Molecular Biology, 11, 1215–1222.CrossRefGoogle Scholar
  182. Wakabayashi, K., Tanji, K., Mori, F., & Takahashi, H. (2007). The Lewy body in Parkinson’s disease: Molecules implicated in the formation and degradation of alpha-synuclein aggregates. Neuropathology, 27, 494–506.PubMedCrossRefGoogle Scholar
  183. Wang, A. M., Miyata, Y., Klinedinst, S., et al. (2013a). Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nature Chemical Biology, 9, 112–118.PubMedCrossRefGoogle Scholar
  184. Wang, J., Wright, H. M., Vempati, P., et al. (2013b). Investigation of nebivolol as a novel therapeutic agent for the treatment of Alzheimer’s disease. Journal of Alzheimer’s Disease, 33, 1147–1156.PubMedCrossRefGoogle Scholar
  185. Wang, H., Tan, M. S., Lu, R. C., Yu, J. T., & Tan, L. (2014a). Heat shock proteins at the crossroads between cancer and Alzheimer’s disease. Biomedical Research International, 2014, 239164.Google Scholar
  186. Wang, X., Yuan, B., Dong, W., Yang, B., Yang, Y., Lin, X., & Gong, G. (2014b). Induction of heat-shock protein 70 expression by geranylgeranylacetone shows cytoprotective effects in cardiomyocytes of mice under humid heat stress. PLoS One, 9, e93536.PubMedPubMedCentralCrossRefGoogle Scholar
  187. Warrick, J. M., Chan, H. Y., Gray-Board, G. L., Chai, Y., Paulson, H. L., & Bonini, N. M. (1999). Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nature Genetics, 23, 425–428.PubMedCrossRefPubMedCentralGoogle Scholar
  188. Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Tanaka, F., Inukai, A., Doyu, M., & Sobue, G. (2005). 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nature Medicine, 11, 1088–1095.PubMedCrossRefPubMedCentralGoogle Scholar
  189. Wentzell, J., & Kretzschmar, D. (2010). Alzheimer’s disease and tauopathy studies in flies and worms. Neurobiology of Disease, 40, 21–28.PubMedPubMedCentralCrossRefGoogle Scholar
  190. West, R. J., Elliott, C. J., & Wade, A. R. (2015). Classification of Parkinson’s disease genotypes in Drosophila using spatiotemporal profiling of vision. Scientific Reports, 5, 16933.PubMedPubMedCentralCrossRefGoogle Scholar
  191. Wilhelmus, M. M., de Waal, R. M., & Verbeek, M. M. (2007). Heat shock proteins and amateur chaperones in amyloid-Beta accumulation and clearance in Alzheimer’s disease. Molecular Neurobiology, 35, 203–216.PubMedPubMedCentralCrossRefGoogle Scholar
  192. Witt, S. N. (2009). Hsp70 molecular chaperones and Parkinson’s disease. Biopolymers, 93, 218–228.CrossRefGoogle Scholar
  193. Witt, S. N. (2010). Hsp70 molecular chaperones and Parkinson’s disease. Biopolymers, 93, 218–228.PubMedCrossRefPubMedCentralGoogle Scholar
  194. Wittmann, C. W., Wszolek, M. F., Shulman, J. M., Salvaterra, P. M., Lewis, J., Hutton, M., & Feany, M. B. (2001). Tauopathy in Drosophila: Neurodegeneration without neurofibrillary tangles. Science, 293, 711–714.PubMedCrossRefPubMedCentralGoogle Scholar
  195. Wolfgang, W. J., Miller, T. W., Webster, J. M., Huston, J. S., Thompson, L. M., Marsh, J. L., & Messer, A. (2005). Suppression of Huntington’s disease pathology in Drosophila by human single-chain Fv antibodies. Proceedings of the National Academy of Sciences of the United States of America, 102, 11563–11568.PubMedPubMedCentralCrossRefGoogle Scholar
  196. Wyss-Coray, T., Lin, C., Yan, F., Yu, G. Q., Rohde, M., McConlogue, L., Masliah, E., & Mucke, L. (2001). TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nature Medicine, 7, 612–618.PubMedCrossRefPubMedCentralGoogle Scholar
  197. Wyttenbach, A., Sauvageot, O., Carmichael, J., Diaz-Latoud, C., Arrigo, A. P., & Rubinsztein, D. C. (2002). Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Human Molecular Genetics, 11, 1137–1151.PubMedCrossRefPubMedCentralGoogle Scholar
  198. Yang, J., Bridges, K., Chen, K. Y., & Liu, A. Y. (2008). Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection. PLoS One, 3, e2864.PubMedPubMedCentralCrossRefGoogle Scholar
  199. Yoo, L., & Chung, K. C. (2018). The ubiquitin E3 ligase CHIP promotes proteasomal degradation of the serine/threonine protein kinase PINK1 during staurosporine-induced cell death. Journal of Biological Chemistry, 293, 1286–1297.PubMedCrossRefPubMedCentralGoogle Scholar
  200. Zhang, C. W., Adeline, H. B., Chai, B. H., Hong, E. T., Ng, C. H., & Lim, K. L. (2016). Pharmacological or genetic activation of Hsp70 protects against loss of Parkin function. Neurodegenerative Diseases, 16, 304–316.PubMedCrossRefPubMedCentralGoogle Scholar
  201. Zhang, Y. Q., & Sarge, K. D. (2007). Celastrol inhibits polyglutamine aggregation and toxicity though induction of the heat shock response. Jouranl Molecular Medicine (Berl), 85, 1421–1428.CrossRefGoogle Scholar
  202. Zheng, Q., Huang, C., Guo, J., Tan, J., Wang, C., Tang, B., & Zhang, H. (2018). Hsp70 participates in PINK1-mediated mitophagy by regulating the stability of PINK1. Neuroscience Letters, 662, 264–270.PubMedCrossRefPubMedCentralGoogle Scholar
  203. Zhu, X., Zhao, X., Burkholder, W. F., Gragerov, A., Ogata, C. M., Gottesman, M. E., & Hendrickson, W. A. (1996). Structural analysis of substrate binding by the molecular chaperone DnaK. Science, 272, 1606–1614.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Genetics & Developmental Biology Laboratory, School of Biological Sciences & BiotechnologyIndian Institute of Advanced Research/IAR, Koba Institutional AreaGandhinagarIndia

Personalised recommendations