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Pathophysiological Roles of Intracellular Proteases in Neuronal Development and Neurological Diseases

  • Tatsurou Yagami
  • Yasuhiro Yamamoto
  • Hiromi Koma
Article

Abstract

Proteases are classified into six distinct classes (cysteine, serine, threonine, aspartic, glutamic, and metalloproteases) on the basis of catalytic mechanism. The cellular control of protein quality senses misfolded or damaged proteins principally by selective ubiquitin-proteasome pathway and non-selective autophagy-lysosome pathway. The two pathways do not only maintain cell homeostasis physiologically, but also mediate necrosis and apoptosis pathologically. Proteasomes are threonine proteases, whereas cathepsins are lysosomal aspartic proteases. Calpains are non-lysosomal cysteine proteases and calcium-dependent papain-like enzyme. Calpains and cathepsins are involved in the neuronal necrosis, which are accidental cell death. Necrosis is featured by the disruption of plasma membranes and lysosomes, the loss of ATP and ribosomes, the lysis of cell and nucleus, and the caspase-independent DNA fragmentation. On the other hand, caspases are cysteine endoproteases and mediate neuronal cell death such as apoptosis and pyroptosis, which are programmed cell death. In the central nervous system, necroptosis, ferroptosis and autophagic cell death are also classified into programmed cell death. Neuronal apoptosis is characterized by cell shrinkage, plasma membrane blebbing, karyorrhexis, chromatin condensation, and DNA fragmentation. Necroptosis and pyroptosis are necrotic and lytic forms of programmed cell death, respectively. Although autophagy is involved in cell survival, it fails to maintain cellular homeostasis, resulting in autophagic cell death. Ferroptosis is induced by reactive oxygen species in excitotoxicity of glutamate and ischemia-reperfusion. Apoptosis and pyroptosis are dependent on caspase-3 and caspase-1, respectively. Autophagic cell death and necroptosis are dependent on calpain and cathepsin, respectively, but independent of caspase. Although apoptosis has been defined by the absence of morphological features of necrosis, the two deaths are both parts of a continuum. The intracellular proteases do not only maintain cell homeostasis but also regulate neuronal maturation during the development of embryonic brain. Furthermore, neurodegenerative diseases are caused by the impairment of quality control mechanisms for a proper folding and function of protein.

Keywords

Neuronal cell death Apoptosis Autophagy Ferroptosis Necrosis Necroptosis Oncosis Pyroptosis 

Abbreviations

AA

Arachidonic acid

Amyloid β

ACD

Autophagic cell death

AD

Alzheimer’s disease

AIF

Apoptosis-inducing factor

ALP

Autophagy–lysosome pathway

ALS

Amyotrophic lateral sclerosis

APP

Amyloid precursor protein

ASC

Apoptosis specific-like adaptor protein

Atg

Autophagy-related genes

AVs

Autophagic vacuoles

[Ca2+]i

Intracellular calcium level

CARD

Caspase recruitment domain

CJD

Creutzfeldt–Jakob disease

CMA

Chaperone-mediated autophagy

CNS

Central nervous system

CRTH2

Chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells

CTX

Cerebral cortex

COX

Cyclooxygenase

CycPGs

Cyclopentenone prostaglandins

Cyt

Cytochrome

DAMP

Danger-associated molecular patterns

DISC

Death-inducing signaling complex

ER

Endoplasmic reticulum

ERK

Extracellular signal-regulated kinase

FADD

Fas-associated death domain

GPX4

Glutathione peroxidase-4

GSH

Glutathione

HD

Huntington’s disease

HPC

Hippocampus

JNK

c-Jun N2-terminal kinase

LOX

Lipoxygenase

L-VDCC

L-type voltage-dependent Ca2+ channels

MAPK

Mitogen-activated protein kinase

MCA

Middle cerebral artery

mTOR

Mammalian target of rapamycin

MLKL

Mixed-lineage kinase domain-like protein

MPTP

Mitochondrial permeability transition pore

NFTs

Neurofibrillary tangles

NGF

Nerve growth factor

NLR

Nucleotide-binding oligomerization domain-like receptor

NOX

NADPH oxygenase

NTRs

Neurotrophic receptors

PAMP

Pathogen-associated molecular patterns

PARP

Poly(ADP-ribose) polymerase

PCD

Programmed cell death

PD

Parkinson’s disease

PI

Propidium iodide

PI3K

Phosphatidylinositol 3-kinase

PPARγ

Peroxisome proliferator-activated receptor-γ

PrPC

Cellular prion protein

PrPSc

Scrapie prion protein

PRRs

Pattern-recognition receptors

PS

Phosphatidylserine

PUMA

p53 upregulated modulator of apoptosis

ROS

Reactive oxygen species

RIP

Receptor-interacting protein

SOD

Superoxide dismutase

sPLA2

Secreted phospholipase A2

STR

Striatum

TNF-α

Tumor necrosis factor α

TRAIL

TNF-related apoptosis-inducing ligand

ULK1

Unc-51 like autophagy activating kinase1

UPP

Ubiquitin–proteasome pathway

UPR

Unfolded protein response

VSC

Ventral spinal cord

15d-PGJ2

15-deoxy-Δ12,14 prostaglandin J2

Notes

Acknowledgments

The work presented in the submitted manuscript was funded by Grant-in-Aid 17K08327 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

References

  1. 1.
    Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12(9):814–822.  https://doi.org/10.1038/ncb0910-814 PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Rosello A, Warnes G, Meier UC (2012) Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die—that is the question. Clin Exp Immunol 168(1):52–57.  https://doi.org/10.1111/j.1365-2249.2011.04544.x PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10(7):458–467.  https://doi.org/10.1038/nrm2708 PubMedCrossRefGoogle Scholar
  4. 4.
    De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492.  https://doi.org/10.1146/annurev.ph.28.030166.002251 PubMedCrossRefGoogle Scholar
  5. 5.
    Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479.  https://doi.org/10.1146/annurev.biochem.67.1.425 PubMedCrossRefGoogle Scholar
  6. 6.
    Ciechanover A (2006) The ubiquitin proteolytic system: from a vague idea, through basic mechanisms, and onto human diseases and drug targeting. Neurology 66(2 Suppl 1):S7–S19.  https://doi.org/10.1212/01.wnl.0000192261.02023.b8 PubMedCrossRefGoogle Scholar
  7. 7.
    Lopez-Salon M, Alonso M, Vianna MR, Viola H, Mello e Souza T, Izquierdo I, Pasquini JM, Medina JH (2001) The ubiquitin–proteasome cascade is required for mammalian long-term memory formation. Eur J Neurosci 14(11):1820–1826PubMedCrossRefGoogle Scholar
  8. 8.
    Tseng BP, Green KN, Chan JL, Blurton-Jones M, LaFerla FM (2008) Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging 29(11):1607–1618.  https://doi.org/10.1016/j.neurobiolaging.2007.04.014 PubMedCrossRefGoogle Scholar
  9. 9.
    Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and down syndrome. Proc Natl Acad Sci U S A 82(12):4245–4249PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Braak H, Braak E, Grundke-Iqbal I, Iqbal K (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65(3):351–355PubMedCrossRefGoogle Scholar
  11. 11.
    Wang Z, Aris VM, Ogburn KD, Soteropoulos P, Figueiredo-Pereira ME (2006) Prostaglandin J2 alters pro-survival and pro-death gene expression patterns and 26 S proteasome assembly in human neuroblastoma cells. J Biol Chem 281(30):21377–21386.  https://doi.org/10.1074/jbc.M601201200 PubMedCrossRefGoogle Scholar
  12. 12.
    Mullally JE, Moos PJ, Edes K, Fitzpatrick FA (2001) Cyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway. J Biol Chem 276(32):30366–30373.  https://doi.org/10.1074/jbc.M102198200 PubMedCrossRefGoogle Scholar
  13. 13.
    Arnaud LT, Myeku N, Figueiredo-Pereira ME (2009) Proteasome-caspase-cathepsin sequence leading to tau pathology induced by prostaglandin J2 in neuronal cells. J Neurochem 110(1):328–342.  https://doi.org/10.1111/j.1471-4159.2009.06142.x PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Tovar-y-Romo LB, Penagos-Puig A, Ramirez-Jarquin JO (2016) Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate. J Neurochem 136(1):13–27.  https://doi.org/10.1111/jnc.13362 PubMedCrossRefGoogle Scholar
  15. 15.
    Weerasinghe P, Buja LM (2012) Oncosis: an important non-apoptotic mode of cell death. Exp Mol Pathol 93(3):302–308.  https://doi.org/10.1016/j.yexmp.2012.09.018 PubMedCrossRefGoogle Scholar
  16. 16.
    Yagami T, Kohma H, Yamamoto Y (2012) L-type voltage-dependent calcium channels as therapeutic targets for neurodegenerative diseases. Curr Med Chem 19(28):4816–4827PubMedCrossRefGoogle Scholar
  17. 17.
    Sahara S, Yamashima T (2010) Calpain-mediated Hsp70.1 cleavage in hippocampal CA1 neuronal death. Biochem Biophys Res Commun 393(4):806–811.  https://doi.org/10.1016/j.bbrc.2010.02.087 PubMedCrossRefGoogle Scholar
  18. 18.
    Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, Baehrecke EH, Lenardo MJ (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304(5676):1500–1502.  https://doi.org/10.1126/science.1096645 PubMedCrossRefGoogle Scholar
  19. 19.
    Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D et al (2005) Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 25(3):1025–1040.  https://doi.org/10.1128/MCB.25.3.1025-1040.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Ullman E, Fan Y, Stawowczyk M, Chen HM, Yue Z, Zong WX (2008) Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress. Cell Death Differ 15(2):422–425.  https://doi.org/10.1038/sj.cdd.4402234 PubMedCrossRefGoogle Scholar
  21. 21.
    Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1–RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137(6):1112–1123.  https://doi.org/10.1016/j.cell.2009.05.037 PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL et al (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 19(1):107–120.  https://doi.org/10.1038/cdd.2011.96 PubMedCrossRefGoogle Scholar
  24. 24.
    Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ (1995) Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 374(6524):736–739.  https://doi.org/10.1038/374736a0 PubMedCrossRefGoogle Scholar
  25. 25.
    Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A 95(25):14681–14686PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Miura M, Zhu H, Rotello R, Hartwieg EA, Yuan J (1993) Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75(4):653–660PubMedCrossRefGoogle Scholar
  27. 27.
    Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148(7):2207–2216PubMedGoogle Scholar
  28. 28.
    Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H et al (2008) BAX activation is initiated at a novel interaction site. Nature 455(7216):1076–1081.  https://doi.org/10.1038/nature07396 PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Daugas E, Susin SA, Zamzami N, Ferri KF, Irinopoulou T, Larochette N, Prevost MC, Leber B et al (2000) Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J 14(5):729–739PubMedCrossRefGoogle Scholar
  30. 30.
    Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12(6):611–620PubMedCrossRefGoogle Scholar
  31. 31.
    Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516.  https://doi.org/10.1080/01926230701320337 PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Lanni C, Racchi M, Memo M, Govoni S, Uberti D (2012) p53 at the crossroads between cancer and neurodegeneration. Free Radic Biol Med 52(9):1727–1733.  https://doi.org/10.1016/j.freeradbiomed.2012.02.034 PubMedCrossRefGoogle Scholar
  33. 33.
    Riley T, Sontag E, Chen P, Levine A (2008) Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 9(5):402–412.  https://doi.org/10.1038/nrm2395 PubMedCrossRefGoogle Scholar
  34. 34.
    Niizuma K, Endo H, Chan PH (2009) Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. J Neurochem 109(Suppl 1):133–138.  https://doi.org/10.1111/j.1471-4159.2009.05897.x PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kruse JP, Gu W (2009) Modes of p53 regulation. Cell 137(4):609–622.  https://doi.org/10.1016/j.cell.2009.04.050 PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D'Amelio M, Criollo A, Morselli E et al (2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10(6):676–687.  https://doi.org/10.1038/ncb1730 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137(6):1100–1111.  https://doi.org/10.1016/j.cell.2009.05.021 PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325(5938):332–336.  https://doi.org/10.1126/science.1172308 PubMedCrossRefGoogle Scholar
  39. 39.
    Wu XN, Yang ZH, Wang XK, Zhang Y, Wan H, Song Y, Chen X, Shao J et al (2014) Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis. Cell Death Differ 21(11):1709–1720.  https://doi.org/10.1038/cdd.2014.77 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X (2014) Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 54(1):133–146.  https://doi.org/10.1016/j.molcel.2014.03.003 PubMedCrossRefGoogle Scholar
  41. 41.
    Kawahara A, Ohsawa Y, Matsumura H, Uchiyama Y, Nagata S (1998) Caspase-independent cell killing by Fas-associated protein with death domain. J Cell Biol 143(5):1353–1360PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD et al (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4(5):313–321.  https://doi.org/10.1038/nchembio.83 PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185(8):1481–1486PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Yagami T, Ueda K, Asakura K, Hata S, Kuroda T, Sakaeda T, Takasu N, Tanaka K et al (2002) Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis. Mol Pharmacol 61(1):114–126PubMedCrossRefGoogle Scholar
  45. 45.
    Brennan MA, Cookson BT (2000) Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol 38(1):31–40PubMedCrossRefGoogle Scholar
  46. 46.
    Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265(1):130–142.  https://doi.org/10.1111/imr.12287 PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Kepp O, Galluzzi L, Zitvogel L, Kroemer G (2010) Pyroptosis—a cell death modality of its kind? Eur J Immunol 40(3):627–630.  https://doi.org/10.1002/eji.200940160 PubMedCrossRefGoogle Scholar
  48. 48.
    Hersh D, Monack DM, Smith MR, Ghori N, Falkow S, Zychlinsky A (1999) The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc Natl Acad Sci U S A 96(5):2396–2401PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3(3):285–296PubMedCrossRefGoogle Scholar
  50. 50.
    Tan S, Sagara Y, Liu Y, Maher P, Schubert D (1998) The regulation of reactive oxygen species production during programmed cell death. J Cell Biol 141(6):1423–1432PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E et al (2008) Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8(3):237–248.  https://doi.org/10.1016/j.cmet.2008.07.005 PubMedCrossRefGoogle Scholar
  52. 52.
    Neitemeier S, Jelinek A, Laino V, Hoffmann L, Eisenbach I, Eying R, Ganjam GK, Dolga AM et al (2017) BID links ferroptosis to mitochondrial cell death pathways. Redox Biol 12:558–570.  https://doi.org/10.1016/j.redox.2017.03.007 PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Tobaben S, Grohm J, Seiler A, Conrad M, Plesnila N, Culmsee C (2011) Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons. Cell Death Differ 18(2):282–292.  https://doi.org/10.1038/cdd.2010.92 PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072.  https://doi.org/10.1016/j.cell.2012.03.042 PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I et al (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447(7146):864–868.  https://doi.org/10.1038/nature05859 PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Speer RE, Karuppagounder SS, Basso M, Sleiman SF, Kumar A, Brand D, Smirnova N, Gazaryan I et al (2013) Hypoxia-inducible factor prolyl hydroxylases as targets for neuroprotection by "antioxidant" metal chelators: from ferroptosis to stroke. Free Radic Biol Med 62:26–36.  https://doi.org/10.1016/j.freeradbiomed.2013.01.026 PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Denton D, Nicolson S, Kumar S (2012) Cell death by autophagy: facts and apparent artefacts. Cell Death Differ 19(1):87–95.  https://doi.org/10.1038/cdd.2011.146 PubMedCrossRefGoogle Scholar
  58. 58.
    Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, Rao Pariti RK, Cieslar-Pobuda A et al (2013) Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Biochim Biophys Acta 1833(9):2057–2069.  https://doi.org/10.1016/j.bbamcr.2013.04.011 PubMedCrossRefGoogle Scholar
  59. 59.
    Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534.  https://doi.org/10.1038/sj.cdd.4401777 PubMedCrossRefGoogle Scholar
  60. 60.
    Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8(9):741–752.  https://doi.org/10.1038/nrm2239 PubMedCrossRefGoogle Scholar
  61. 61.
    Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L, Kroemer G (2007) Cell death modalities: classification and pathophysiological implications. Cell Death Differ 14(7):1237–1243.  https://doi.org/10.1038/sj.cdd.4402148 PubMedCrossRefGoogle Scholar
  62. 62.
    Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140(3):313–326.  https://doi.org/10.1016/j.cell.2010.01.028 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736.  https://doi.org/10.1146/annurev.neuro.24.1.677 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294(5548):1945–1948.  https://doi.org/10.1126/science.1065057 PubMedCrossRefGoogle Scholar
  65. 65.
    Bhakar AL, Howell JL, Paul CE, Salehi AH, Becker EB, Said F, Bonni A, Barker PA (2003) Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of bad. J Neurosci 23(36):11373–11381PubMedCrossRefGoogle Scholar
  66. 66.
    Troy CM, Friedman JE, Friedman WJ (2002) Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases. J Biol Chem 277(37):34295–34302.  https://doi.org/10.1074/jbc.M205167200 PubMedCrossRefGoogle Scholar
  67. 67.
    Coffey ET (2014) Nuclear and cytosolic JNK signalling in neurons. Nat Rev Neurosci 15(5):285–299.  https://doi.org/10.1038/nrn3729 PubMedCrossRefGoogle Scholar
  68. 68.
    Bjorkblom B, Vainio JC, Hongisto V, Herdegen T, Courtney MJ, Coffey ET (2008) All JNKs can kill, but nuclear localization is critical for neuronal death. J Biol Chem 283(28):19704–19713.  https://doi.org/10.1074/jbc.M707744200 PubMedCrossRefGoogle Scholar
  69. 69.
    Oppenheim RW (2001) Viktor Hamburger (1900–2001). Journey of a neuroembryologist to the end of the millennium and beyond. Neuron 31(2):179–190PubMedCrossRefGoogle Scholar
  70. 70.
    Nijholt DA, De Kimpe L, Elfrink HL, Hoozemans JJ, Scheper W (2011) Removing protein aggregates: the role of proteolysis in neurodegeneration. Curr Med Chem 18(16):2459–2476PubMedCrossRefGoogle Scholar
  71. 71.
    Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6(1):79–87.  https://doi.org/10.1038/nrm1552 PubMedCrossRefGoogle Scholar
  72. 72.
    Agostini M, Tucci P, Melino G (2011) Cell death pathology: perspective for human diseases. Biochem Biophys Res Commun 414(3):451–455.  https://doi.org/10.1016/j.bbrc.2011.09.081 PubMedCrossRefGoogle Scholar
  73. 73.
    Hellwig CT, Passante E, Rehm M (2011) The molecular machinery regulating apoptosis signal transduction and its implication in human physiology and pathophysiologies. Curr Mol Med 11(1):31–47PubMedCrossRefGoogle Scholar
  74. 74.
    Ciechanover A (2017) Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin–proteasome system and onto human diseases and drug targeting. Best Pract Res Clin Haematol 30(4):341–355.  https://doi.org/10.1016/j.beha.2017.09.001 PubMedCrossRefGoogle Scholar
  75. 75.
    Yagami T, Yamamoto Y, Koma H (2014) The role of secretory phospholipase a(2) in the central nervous system and neurological diseases. Mol Neurobiol 49(2):863–876.  https://doi.org/10.1007/s12035-013-8565-9 PubMedCrossRefGoogle Scholar
  76. 76.
    Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A et al (2008) Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nat Chem Biol 4(5):295–305.  https://doi.org/10.1038/nchembio.79 PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Uversky VN (2007) Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J Neurochem 103(1):17–37.  https://doi.org/10.1111/j.1471-4159.2007.04764.x PubMedCrossRefGoogle Scholar
  78. 78.
    Griffith JS (1967) Self-replication and scrapie. Nature 215(5105):1043–1044PubMedCrossRefGoogle Scholar
  79. 79.
    Andersen PM, Al-Chalabi A (2011) Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat Rev Neurol 7(11):603–615.  https://doi.org/10.1038/nrneurol.2011.150 PubMedCrossRefGoogle Scholar
  80. 80.
    Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10(12):524–530PubMedCrossRefGoogle Scholar
  81. 81.
    Lee S, Sato Y, Nixon RA (2011) Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer's-like axonal dystrophy. J Neurosci 31(21):7817–7830.  https://doi.org/10.1523/JNEUROSCI.6412-10.2011 PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Hollenbeck PJ (1993) Products of endocytosis and autophagy are retrieved from axons by regulated retrograde organelle transport. J Cell Biol 121(2):305–315PubMedCrossRefGoogle Scholar
  83. 83.
    Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889.  https://doi.org/10.1038/nature04724 PubMedCrossRefGoogle Scholar
  84. 84.
    Keller JN, Huang FF, Markesbery WR (2000) Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience 98(1):149–156PubMedCrossRefGoogle Scholar
  85. 85.
    Guglielmo MA, Chan PT, Cortez S, Stopa EG, McMillan P, Johanson CE, Epstein M, Doberstein CE (1998) The temporal profile and morphologic features of neuronal death in human stroke resemble those observed in experimental forebrain ischemia: the potential role of apoptosis. Neurol Res 20(4):283–296PubMedCrossRefGoogle Scholar
  86. 86.
    Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, Shibanai K, Kominami E, Uchiyama Y (1995) Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 15(2):1001–1011PubMedCrossRefGoogle Scholar
  87. 87.
    Sauer D, Allegrini PR, Cosenti A, Pataki A, Amacker H, Fagg GE (1993) Characterization of the cerebroprotective efficacy of the competitive NMDA receptor antagonist CGP40116 in a rat model of focal cerebral ischemia: an in vivo magnetic resonance imaging study. J Cereb Blood Flow Metab 13(4):595–602.  https://doi.org/10.1038/jcbfm.1993.77 PubMedCrossRefGoogle Scholar
  88. 88.
    Vieira M, Fernandes J, Carreto L, Anuncibay-Soto B, Santos M, Han J, Fernandez-Lopez A, Duarte CB et al (2014) Ischemic insults induce necroptotic cell death in hippocampal neurons through the up-regulation of endogenous RIP3. Neurobiol Dis 68:26–36.  https://doi.org/10.1016/j.nbd.2014.04.002 PubMedCrossRefGoogle Scholar
  89. 89.
    Chu X, Fu X, Zou L, Qi C, Li Z, Rao Y, Ma K (2007) Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia. Brain Res 1149:157–164.  https://doi.org/10.1016/j.brainres.2007.02.061 PubMedCrossRefGoogle Scholar
  90. 90.
    Umemura K, Kawai H, Ishihara H, Nakashima M (1995) Inhibitory effect of clopidogrel, vapiprost and argatroban on the middle cerebral artery thrombosis in the rat. Jpn J Pharmacol 67(3):253–258PubMedCrossRefGoogle Scholar
  91. 91.
    Hallenbeck JM (1994) Blood-damaged tissue interaction in experimental brain ischemia. Acta Neurochir Suppl 60:233–237PubMedGoogle Scholar
  92. 92.
    Li Y, Sharov VG, Jiang N, Zaloga C, Sabbah HN, Chopp M (1995) Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146(5):1045–1051PubMedPubMedCentralGoogle Scholar
  93. 93.
    Yagami T, Ueda K, Asakura K, Sakaeda T, Hata S, Kuroda T, Sakaguchi G, Itoh N et al (2003) Porcine pancreatic group IB secretory phospholipase A2 potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels. Brain Res 960(1–2):71–80PubMedCrossRefGoogle Scholar
  94. 94.
    Yagami T, Ueda K, Asakura K, Nakazato H, Hata S, Kuroda T, Sakaeda T, Sakaguchi G et al (2003) Human group IIA secretory phospholipase A2 potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels in cultured rat cortical neurons. J Neurochem 85(3):749–758PubMedCrossRefGoogle Scholar
  95. 95.
    Yagami T, Ueda K, Hata S, Kuroda T, Itoh N, Sakaguchi G, Okamura N, Sakaeda T et al (2005) S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase a(2)-induced apoptosis. Neuropharmacology 49(2):174–184.  https://doi.org/10.1016/j.neuropharm.2005.02.011 PubMedCrossRefGoogle Scholar
  96. 96.
    Nicholls DG (2009) Mitochondrial calcium function and dysfunction in the central nervous system. Biochim Biophys Acta 1787(11):1416–1424.  https://doi.org/10.1016/j.bbabio.2009.03.010 PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Polster BM, Basanez G, Etxebarria A, Hardwick JM, Nicholls DG (2005) Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem 280(8):6447–6454.  https://doi.org/10.1074/jbc.M413269200 PubMedCrossRefGoogle Scholar
  98. 98.
    Zhang WH, Wang X, Narayanan M, Zhang Y, Huo C, Reed JC, Friedlander RM (2003) Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Proc Natl Acad Sci U S A 100(26):16012–16017.  https://doi.org/10.1073/pnas.2534856100 PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T et al (2004) The role of autophagy during the early neonatal starvation period. Nature 432(7020):1032–1036.  https://doi.org/10.1038/nature03029 PubMedCrossRefGoogle Scholar
  100. 100.
    Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, Lorenz JN, Dunn RS, Vorhees CV et al (2006) Cerebral ischemia–hypoxia induces intravascular coagulation and autophagy. Am J Pathol 169(2):566–583.  https://doi.org/10.2353/ajpath.2006.051066 PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, Kawahara N, Kuida K et al (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol 172(2):454–469.  https://doi.org/10.2353/ajpath.2008.070876 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Davila D, Torres-Aleman I (2008) Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell 19(5):2014–2025.  https://doi.org/10.1091/mbc.E07-08-0811 PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Wisniewski T, Frangione B (1996) Molecular biology of brain aging and neurodegenerative disorders. Acta Neurobiol Exp (Wars) 56(1):267–279Google Scholar
  104. 104.
    Giraldo E, Lloret A, Fuchsberger T, Vina J (2014) Abeta and tau toxicities in Alzheimer's are linked via oxidative stress-induced p38 activation: protective role of vitamin E. Redox Biol 2:873–877.  https://doi.org/10.1016/j.redox.2014.03.002 PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 8(6):595–608.  https://doi.org/10.15252/emmm.201606210 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci U S A 84(9):3033–3036PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 64(2):113–122PubMedCrossRefGoogle Scholar
  108. 108.
    Yagami T (2006) Cerebral arachidonate cascade in dementia: Alzheimer's disease and vascular dementia. Curr Neuropharmacol 4(1):87–100PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Lin TN, Wang Q, Simonyi A, Chen JJ, Cheung WM, He YY, Xu J, Sun AY et al (2004) Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain. J Neurochem 90(3):637–645PubMedCrossRefGoogle Scholar
  110. 110.
    Moses GS, Jensen MD, Lue LF, Walker DG, Sun AY, Simonyi A, Sun GY (2006) Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease. J Neuroinflammation 3:28.  https://doi.org/10.1186/1742-2094-3-28 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci 31(9):454–463PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K (1997) Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals. J Neurochem 68(1):265–271PubMedCrossRefGoogle Scholar
  113. 113.
    Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE (1992) Beta-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12(2):376–389PubMedCrossRefGoogle Scholar
  114. 114.
    Ueda K, Fukui Y, Kageyama H (1994) Amyloid beta protein-induced neuronal cell death: neurotoxic properties of aggregated amyloid beta protein. Brain Res 639(2):240–244PubMedCrossRefGoogle Scholar
  115. 115.
    Viola HM, Arthur PG, Hool LC (2007) Transient exposure to hydrogen peroxide causes an increase in mitochondria-derived superoxide as a result of sustained alteration in L-type Ca2+ channel function in the absence of apoptosis in ventricular myocytes. Circ Res 100(7):1036–1044PubMedCrossRefGoogle Scholar
  116. 116.
    Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H et al (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767PubMedCrossRefGoogle Scholar
  117. 117.
    Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D, Zaccheo D, Odetti P et al (2000) Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun 268(2):642–646PubMedCrossRefGoogle Scholar
  118. 118.
    Harada J, Sugimoto M (1999) Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons. Brain Res 842(2):311–323PubMedCrossRefGoogle Scholar
  119. 119.
    Lee C, Park DW, Lee J, Lee TI, Kim YJ, Lee YS, Baek SH (2006) Secretory phospholipase A2 induces apoptosis through TNF-alpha and cytochrome c-mediated caspase cascade in murine macrophage RAW 264.7 cells. Eur J Pharmacol 536(1–2):47–53PubMedCrossRefGoogle Scholar
  120. 120.
    Fahnestock M, Michalski B, Xu B, Coughlin MD (2001) The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease. Mol Cell Neurosci 18(2):210–220.  https://doi.org/10.1006/mcne.2001.1016 PubMedCrossRefGoogle Scholar
  121. 121.
    Sobottka B, Reinhardt D, Brockhaus M, Jacobsen H, Metzger F (2008) ProNGF inhibits NGF-mediated TrkA activation in PC12 cells. J Neurochem 107(5):1294–1303.  https://doi.org/10.1111/j.1471-4159.2008.05690.x PubMedCrossRefGoogle Scholar
  122. 122.
    Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276(5321):2045–2047PubMedCrossRefGoogle Scholar
  123. 123.
    Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840.  https://doi.org/10.1038/42166 PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Duarte MH, Tone LG, Soares LR, dos Santos SA (1990) Cytogenetic study of a case of childhood erythroleukemia. Cancer Genet Cytogenet 49(1):25–30PubMedCrossRefGoogle Scholar
  125. 125.
    Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216(4542):136–144PubMedCrossRefGoogle Scholar
  126. 126.
    Saborio GP, Permanne B, Soto C (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411(6839):810–813.  https://doi.org/10.1038/35081095 PubMedCrossRefGoogle Scholar
  127. 127.
    Boellaard JW, Kao M, Schlote W, Diringer H (1991) Neuronal autophagy in experimental scrapie. Acta Neuropathol 82(3):225–228PubMedCrossRefGoogle Scholar
  128. 128.
    Yagami T, Koma H, Yamamoto Y (2016) Pathophysiological roles of cyclooxygenases and prostaglandins in the central nervous system. Mol Neurobiol 53(7):4754–4771.  https://doi.org/10.1007/s12035-015-9355-3 PubMedCrossRefGoogle Scholar
  129. 129.
    Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD et al (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18(2):327–338PubMedCrossRefGoogle Scholar
  130. 130.
    Leigh PN, Whitwell H, Garofalo O, Buller J, Swash M, Martin JE, Gallo JM, Weller RO et al (1991) Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 114(Pt 2):775–788PubMedCrossRefGoogle Scholar
  131. 131.
    Friedlander RM, Brown RH, Gagliardini V, Wang J, Yuan J (1997) Inhibition of ICE slows ALS in mice. Nature 388(6637):31.  https://doi.org/10.1038/40299 PubMedCrossRefGoogle Scholar
  132. 132.
    Tovar YRLB, Tapia R (2010) VEGF protects spinal motor neurons against chronic excitotoxic degeneration in vivo by activation of PI3-K pathway and inhibition of p38MAPK. J Neurochem 115(5):1090–1101.  https://doi.org/10.1111/j.1471-4159.2010.06766.x CrossRefGoogle Scholar
  133. 133.
    Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr (1985) Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 44(6):559–577PubMedCrossRefGoogle Scholar
  134. 134.
    Li H, Li SH, Johnston H, Shelbourne PF, Li XJ (2000) Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat Genet 25(4):385–389.  https://doi.org/10.1038/78054 PubMedCrossRefGoogle Scholar
  135. 135.
    Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington's disease. Eur J Neurosci 27(11):2803–2820.  https://doi.org/10.1111/j.1460-9568.2008.06310.x PubMedCrossRefGoogle Scholar
  136. 136.
    Yagami T, Ueda K, Asakura K, Hayasaki-Kajiwara Y, Nakazato H, Sakaeda T, Hata S, Kuroda T et al (2002) Group IB secretory phospholipase A2 induces neuronal cell death via apoptosis. J Neurochem 81(3):449–461PubMedCrossRefGoogle Scholar
  137. 137.
    Yagami T, Yamamoto Y, Koma H (2017) Physiological and pathological roles of 15-deoxy-Delta12,14-prostaglandin J2 in the central nervous system and neurological diseases. Mol Neurobiol 55:2227–2248.  https://doi.org/10.1007/s12035-017-0435-4 PubMedCrossRefGoogle Scholar
  138. 138.
    Iwamoto N, Kobayashi K, Kosaka K (1989) The formation of prostaglandins in the postmortem cerebral cortex of Alzheimer-type dementia patients. J Neurol 236(2):80–84PubMedCrossRefGoogle Scholar
  139. 139.
    Gaudet RJ, Alam I, Levine L (1980) Accumulation of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion. J Neurochem 35(3):653–658PubMedCrossRefGoogle Scholar
  140. 140.
    Fitzpatrick FA, Wynalda MA (1983) Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro. J Biol Chem 258(19):11713–11718PubMedGoogle Scholar
  141. 141.
    Shibata T, Kondo M, Osawa T, Shibata N, Kobayashi M, Uchida K (2002) 15-deoxy-delta 12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. J Biol Chem 277(12):10459–10466.  https://doi.org/10.1074/jbc.M110314200 PubMedCrossRefGoogle Scholar
  142. 142.
    Yagami T, Ueda K, Asakura K, Takasu N, Sakaeda T, Itoh N, Sakaguchi G, Kishino J et al (2003) Novel binding sites of 15-deoxy-Delta12,14-prostaglandin J2 in plasma membranes from primary rat cortical neurons. Exp Cell Res 291(1):212–227PubMedCrossRefGoogle Scholar
  143. 143.
    Yagami T, Yamamoto Y, Koma H (2017) 15-deoxy-Delta12,14-prostaglandin J2 in neurodegenerative diseases and cancers. Oncotarget 8(6):9007–9008.  https://doi.org/10.18632/oncotarget.14701 PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Koma H, Yamamoto Y, Nishii A, Yagami T (2017) 15-deoxy-Delta12,14-prostaglandin J2 induced neurotoxicity via suppressing phosphoinositide 3-kinase. Neuropharmacology 113(Pt a):416–425.  https://doi.org/10.1016/j.neuropharm.2016.10.017 PubMedCrossRefGoogle Scholar
  145. 145.
    Figueiredo-Pereira ME, Rockwell P, Schmidt-Glenewinkel T, Serrano P (2014) Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin–proteasome pathway and mitochondria to neurodegeneration. Front Mol Neurosci 7:104.  https://doi.org/10.3389/fnmol.2014.00104 PubMedCrossRefGoogle Scholar
  146. 146.
    Asai A, Tanahashi N, Qiu JH, Saito N, Chi S, Kawahara N, Tanaka K, Kirino T (2002) Selective proteasomal dysfunction in the hippocampal CA1 region after transient forebrain ischemia. J Cereb Blood Flow Metab 22(6):705–710.  https://doi.org/10.1097/00004647-200206000-00009 PubMedCrossRefGoogle Scholar
  147. 147.
    Kawasaki H, Murayama S, Tomonaga M, Izumiyama N, Shimada H (1987) Neurofibrillary tangles in human upper cervical ganglia. Morphological study with immunohistochemistry and electron microscopy. Acta Neuropathol 75(2):156–159PubMedCrossRefGoogle Scholar
  148. 148.
    Love S, Saitoh T, Quijada S, Cole GM, Terry RD (1988) Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, pick bodies and Lewy bodies. J Neuropathol Exp Neurol 47(4):393–405PubMedCrossRefGoogle Scholar
  149. 149.
    Kilic E, Kilic U, Wang Y, Bassetti CL, Marti HH, Hermann DM (2006) The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia. FASEB J 20(8):1185–1187.  https://doi.org/10.1096/fj.05-4829fje PubMedCrossRefGoogle Scholar
  150. 150.
    Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A (2001) Alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block a beta-amyloid-induced neurotoxicity. J Biol Chem 276(17):13541–13546.  https://doi.org/10.1074/jbc.M008035200 PubMedCrossRefGoogle Scholar
  151. 151.
    Sagi Y, Mandel S, Amit T, Youdim MB (2007) Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 25(1):35–44.  https://doi.org/10.1016/j.nbd.2006.07.020 PubMedCrossRefGoogle Scholar
  152. 152.
    Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15(4):961–973PubMedCrossRefGoogle Scholar
  153. 153.
    Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, Tsujimoto Y (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6(12):1221–1228.  https://doi.org/10.1038/ncb1192 PubMedCrossRefGoogle Scholar
  154. 154.
    Yamamoto Y, Koma H, Yagami T (2015) Hydrogen peroxide mediated the neurotoxicity of an antibody against plasmalemmal neuronspecific enolase in primary cortical neurons. Neurotoxicology 49:86–93.  https://doi.org/10.1016/j.neuro.2015.05.008 PubMedCrossRefGoogle Scholar
  155. 155.
    Yamamoto Y, Koma H, Yagami T (2015) Localization of 14-3-3delta/xi on the neuronal cell surface. Exp Cell Res 338(2):149–161.  https://doi.org/10.1016/j.yexcr.2015.09.002 PubMedCrossRefGoogle Scholar
  156. 156.
    Yamamoto Y, Koma H, Nishii S, Yagami T (2017) Anti-heat shock 70 kDa protein antibody induced neuronal cell death. Biol Pharm Bull 40(4):402–412.  https://doi.org/10.1248/bpb.b16-00641 PubMedCrossRefGoogle Scholar
  157. 157.
    Wang W, Gao C, Hou XY, Liu Y, Zong YY, Zhang GY (2004) Activation and involvement of JNK1/2 in hydrogen peroxide-induced neurotoxicity in cultured rat cortical neurons. Acta Pharmacol Sin 25(5):630–636PubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Himeji Dokkyo UniversityHimejiJapan

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