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Molecular and Cellular Insights: Neuroinflammation and Amyotrophic Lateral Sclerosis

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Inflammation: the Common Link in Brain Pathologies

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Abstract

Accumulation of misfolded and abnormal proteins generates probably a common and complex pathomechanism in various neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis, and Prion) and in aging. In amyotrophic lateral sclerosis (ALS), neuroinflammation appears in the form of T-lymphocyte infiltration, presence of reactive astroglial and microglial cells. Most likely, end stage of this toxic cascade results in death of motor neurons in the cortex, brainstem, and spinal cord. More than 10 different genetic causes of familial ALS are known; but still it is a challenge to prevent the loss of descending motor tracts by suppressing the degeneration of motor neurons. This chapter will focus on the precise understanding of neuroinflammatory responses in molecular pathomechanism of ALS and it also discusses new potential therapeutic strategies to improve neuroprotection and to alleviate proteotoxicity in ALS linked motor neurodegeneration.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ANG:

Angiogenin

BBB:

Blood brain barrier

Bcl-2:

B-cell lymphoma 2

C9orf72:

Chromosome 9 open reading frame 72

CHIP:

Carboxy terminus of Hsp70-interacting protein

CNS:

Central nervous system

EAAT2:

Excitatory amino acid transporter 2

fALS:

Familial amyotrophic lateral sclerosis

FTD:

Frontotemporal dementia

FUS:

Fused in sarcoma

GDNF:

Glial cell-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

Hsp70:

Heat shock protein70

IFN-γ:

Interferon-γ

IL:

Interleukins

MRI:

Magnetic resonance imaging

NG2+ :

Neuron-glial antigen 2-positive

NMDA:

N-methyl-D-aspartic acid

PET:

Positron emission tomography

PNS:

Peripheral nervous system

PGC-1α:

Peroxisome proliferator-activated receptor gamma (PPAR-γ) coactivator-1α

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SETX:

Senataxin

SOD-1:

Superoxide dismutase 1

TDP-43:

Transactive response DNA binding protein-43

TNF-α:

Tumor necrosis factor-α

UPS:

Ubiquitin proteasome system

VAPB:

Vesicle-associated membrane protein-associated protein B

References

  • Abe K, Takanashi M, Watanabe Y, Tanaka H, Fujita N, Hirabuki N, Yanagihara T (2001) Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis. Neuroradiology 43(7):537–541

    Article  CAS  PubMed  Google Scholar 

  • Abrahams S, Newton J, Niven E, Foley J, Bak TH (2014) Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener 15(1–2):9–14. doi:10.3109/21678421.2013.805784

    Article  PubMed  Google Scholar 

  • Al-Chalabi A, Jones A, Troakes C, King A, Al-Sarraj S, van den Berg LH (2012) The genetics and neuropathology of amyotrophic lateral sclerosis. Acta Neuropathol 124(3):339–352. doi:10.1007/s00401-012-1022-4

    Article  CAS  PubMed  Google Scholar 

  • Alfahad T, Nath A (2013) Retroviruses and amyotrophic lateral sclerosis. Antiviral Res 99(2):180–187. doi:10.1016/j.antiviral.2013.05.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almer G, Vukosavic S, Romero N, Przedborski S (1999) Inducible nitric oxide synthase up-regulation in a transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 72(6):2415–2425

    Article  CAS  PubMed  Google Scholar 

  • Aloisi F (2001) Immune function of microglia. Glia 36(2):165–179

    Article  CAS  PubMed  Google Scholar 

  • Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351(3):602–611. doi:10.1016/j.bbrc.2006.10.093

    Article  CAS  PubMed  Google Scholar 

  • Baumer D, Talbot K, Turner MR (2014) Advances in motor neurone disease. J R Soc Med 107(1):14–21. doi:10.1177/0141076813511451

    Article  PubMed  Google Scholar 

  • Bellingham MC (2011) A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci Ther 17(1):4–31. doi:10.1111/j.1755-5949.2009.00116.x

    Article  CAS  PubMed  Google Scholar 

  • Bendotti C, Marino M, Cheroni C, Fontana E, Crippa V, Poletti A, De Biasi S (2012) Dysfunction of constitutive and inducible ubiquitin-proteasome system in amyotrophic lateral sclerosis: implication for protein aggregation and immune response. Prog Neurobiol 97(2):101–126. doi:10.1016/j.pneurobio.2011.10.001

    Article  CAS  PubMed  Google Scholar 

  • Bensimon G, Lacomblez L, Meininger V (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 330(9):585–591. doi:10.1056/NEJM199403033300901

    Article  CAS  PubMed  Google Scholar 

  • Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43(5):1369–1374

    Article  CAS  PubMed  Google Scholar 

  • Bergemalm D, Forsberg K, Jonsson PA, Graffmo KS, Brannstrom T, Andersen PM, Antti H, Marklund SL (2009) Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis. Mol Cell Proteomics 8(6):1306–1317. doi:10.1074/mcp.M900046-MCP200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blokhuis AM, Groen EJ, Koppers M, van den Berg LH, Pasterkamp RJ (2013) Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol 125(6):777–794. doi:10.1007/s00401-013-1125-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boillee S, Vande Velde C, Cleveland DW (2006) ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 52(1):39–59. doi:10.1016/j.neuron.2006.09.018

    Article  CAS  PubMed  Google Scholar 

  • Boylan K, Yang C, Crook J, Overstreet K, Heckman M, Wang Y, Borchelt D, Shaw G (2009) Immunoreactivity of the phosphorylated axonal neurofilament H subunit (pNF-H) in blood of ALS model rodents and ALS patients: evaluation of blood pNF-H as a potential ALS biomarker. J Neurochem 111(5):1182–1191. doi:10.1111/j.1471-4159.2009.06386.x

    Article  CAS  PubMed  Google Scholar 

  • Bros-Facer V, Krull D, Taylor A, Dick JR, Bates SA, Cleveland MS, Prinjha RK, Greensmith L (2014) Treatment with an antibody directed against Nogo-A delays disease progression in the SOD1G93A mouse model of Amyotrophic lateral sclerosis. Hum Mol Genet 23(16):4187–4200. doi:10.1093/hmg/ddu136

    Article  CAS  PubMed  Google Scholar 

  • Bruening W, Roy J, Giasson B, Figlewicz DA, Mushynski WE, Durham HD (1999) Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis. J Neurochem 72(2):693–699

    Article  CAS  PubMed  Google Scholar 

  • Bucchia M, Ramirez A, Parente V, Simone C, Nizzardo M, Magri F, Dametti S, Corti S (2015) Therapeutic development in amyotrophic lateral sclerosis. Clin Ther 37(3):668–680. doi:10.1016/j.clinthera.2014.12.020

    Article  PubMed  Google Scholar 

  • Bunton-Stasyshyn RK, Saccon RA, Fratta P, Fisher EM (2014) SOD1 function and its implications for amyotrophic lateral sclerosis pathology: new and renascent themes. Neuroscientist. doi:10.1177/1073858414561795

    PubMed  Google Scholar 

  • Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G, Doykan CE, Wu PM, Gali RR, Iyer LK, Lawson R, Berry J, Krichevsky AM, Cudkowicz ME, Weiner HL (2012) Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 122(9):3063–3087. doi:10.1172/JCI62636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carri MT, Valle C, Bozzo F, Cozzolino M (2015) Oxidative stress and mitochondrial damage: importance in non-SOD1 ALS. Front Cell Neurosci 9:41. doi:10.3389/fncel.2015.00041

    PubMed  PubMed Central  Google Scholar 

  • Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC (2006) CNS immune privilege: hiding in plain sight. Immunol Rev 213:48–65. doi:10.1111/j.1600-065X.2006.00441.x

    Article  PubMed  PubMed Central  Google Scholar 

  • Chapman MC, Jelsone-Swain L, Johnson TD, Gruis KL, Welsh RC (2014) Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis. J Magn Reson Imaging 39(3):641–647. doi:10.1002/jmri.24218

    Article  PubMed  Google Scholar 

  • Charcot J-M, Joffroy A (1869) Deux cas d’atrophie musculaire progressive avec lésions de la substance grise et des faisceaux antérolatéraux de la moelle épinière. Masson, Paris

    Google Scholar 

  • Chen S, Sayana P, Zhang X, Le W (2013) Genetics of amyotrophic lateral sclerosis: an update. Mol Neurodegener 8:28. doi:10.1186/1750-1326-8-28

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheroni C, Marino M, Tortarolo M, Veglianese P, De Biasi S, Fontana E, Zuccarello LV, Maynard CJ, Dantuma NP, Bendotti C (2009) Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. Hum Mol Genet 18(1):82–96. doi:10.1093/hmg/ddn319

    Article  CAS  PubMed  Google Scholar 

  • Chhangani D, Mishra A (2013) Mahogunin ring finger-1 (MGRN1) suppresses chaperone-associated misfolded protein aggregation and toxicity. Sci Rep 3:1972. doi:10.1038/srep01972

    Article  PubMed  PubMed Central  Google Scholar 

  • Chhangani D, Jana NR, Mishra A (2013) Misfolded proteins recognition strategies of E3 ubiquitin ligases and neurodegenerative diseases. Mol Neurobiol 47(1):302–312. doi:10.1007/s12035-012-8351-0

    Article  CAS  PubMed  Google Scholar 

  • Chhangani D, Upadhyay A, Amanullah A, Joshi V, Mishra A (2014) Ubiquitin ligase ITCH recruitment suppresses the aggregation and cellular toxicity of cytoplasmic misfolded proteins. Sci Rep 4:5077. doi:10.1038/srep05077

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chhangani D, Endo F, Amanullah A, Upadhyay A, Watanabe S, Mishra R, Yamanaka K, Mishra A (2015) Mahogunin ring finger 1 confers cytoprotection against mutant SOD1 aggresomes and is defective in an ALS mouse model. Neurobiol Dis 86:16–28. doi:10.1016/j.nbd.2015.11.017

    Article  PubMed  CAS  Google Scholar 

  • Chio A (1999) ISIS survey: an international study on the diagnostic process and its implications in amyotrophic lateral sclerosis. J Neurol 246(Suppl 3):III1-5

    Google Scholar 

  • Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, Carroll MC (2008) T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci USA 105(46):17913–17918. doi:10.1073/pnas.0804610105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cleveland DW, Rothstein JD (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2(11):806–819. doi:10.1038/35097565

    Article  CAS  PubMed  Google Scholar 

  • Corti S, Nizzardo M, Nardini M, Donadoni C, Salani S, Simone C, Falcone M, Riboldi G, Govoni A, Bresolin N, Comi GP (2010) Systemic transplantation of c-kit+ cells exerts a therapeutic effect in a model of amyotrophic lateral sclerosis. Hum Mol Genet 19(19):3782–3796. doi:10.1093/hmg/ddq293

    Article  CAS  PubMed  Google Scholar 

  • Dale JM, Garcia ML (2012) Neurofilament phosphorylation during development and disease: which came first, the phosphorylation or the accumulation? J Amino Acids 2012:382107. doi:10.1155/2012/382107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2):245–256. doi:10.1016/j.neuron.2011.09.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng HX, Shi Y, Furukawa Y, Zhai H, Fu R, Liu E, Gorrie GH, Khan MS, Hung WY, Bigio EH, Lukas T, Dal Canto MC, O’Halloran TV, Siddique T (2006) Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. Proc Natl Acad Sci USA 103(18):7142–7147. doi:10.1073/pnas.0602046103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deshpande DM, Kim YS, Martinez T, Carmen J, Dike S, Shats I, Rubin LL, Drummond J, Krishnan C, Hoke A, Maragakis N, Shefner J, Rothstein JD, Kerr DA (2006) Recovery from paralysis in adult rats using embryonic stem cells. Ann Neurol 60(1):32–44. doi:10.1002/ana.20901

    Article  CAS  PubMed  Google Scholar 

  • Dewil M, Van Den Bosch L, Robberecht W (2007) Microglia in amyotrophic lateral sclerosis. Acta Neurol Belg 107(3):63–70

    PubMed  Google Scholar 

  • Doble A (1996) The pharmacology and mechanism of action of riluzole. Neurology 47(6 Suppl 4):S233–S241

    Article  CAS  PubMed  Google Scholar 

  • Droppelmann CA, Campos-Melo D, Ishtiaq M, Volkening K, Strong MJ (2014) RNA metabolism in ALS: when normal processes become pathological. Amyotroph Lateral Scler Frontotemporal Degener 15(5–6):321–336. doi:10.3109/21678421.2014.881377

    Article  CAS  PubMed  Google Scholar 

  • Dupuis L, Gonzalez de Aguilar JL, Oudart H, de Tapia M, Barbeito L, Loeffler JP (2004) Mitochondria in amyotrophic lateral sclerosis: a trigger and a target. Neurodegener Dis 1(6):245–254. doi:10.1159/000085063

    Article  PubMed  Google Scholar 

  • Elliott JL (2001) Cytokine upregulation in a murine model of familial amyotrophic lateral sclerosis. Brain Res Mol Brain Res 95(1–2):172–178

    Article  CAS  PubMed  Google Scholar 

  • Endo F, Yamanaka K (2014) Neuroinflammation in amyotrophic lateral sclerosis. Rinsho Shinkeigaku 54(12):1128–1131. doi:10.5692/clinicalneurol.54.1128

    Article  PubMed  Google Scholar 

  • Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28(3):138–145. doi:10.1016/j.it.2007.01.005

    Article  CAS  PubMed  Google Scholar 

  • Federici T, Boulis NM (2012) Gene therapy for amyotrophic lateral sclerosis. Neurobiol Dis 48(2):236–242. doi:10.1016/j.nbd.2011.08.018

    Article  CAS  PubMed  Google Scholar 

  • Finkelstein A, Kunis G, Seksenyan A, Ronen A, Berkutzki T, Azoulay D, Koronyo-Hamaoui M, Schwartz M (2011) Abnormal changes in NKT cells, the IGF-1 axis, and liver pathology in an animal model of ALS. PLoS ONE 6(8):e22374. doi:10.1371/journal.pone.0022374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foran E, Trotti D (2009) Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid Redox Signal 11(7):1587–1602. doi:10.1089/ars.2009.2444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foster E, Tsang BK, Kam A, Storey E, Day B, Hill A (2015) Hirayama disease. J Clin Neurosci 22(6):951–954. doi:10.1016/j.jocn.2014.11.025

    Article  PubMed  Google Scholar 

  • Gaiottino J, Norgren N, Dobson R, Topping J, Nissim A, Malaspina A, Bestwick JP, Monsch AU, Regeniter A, Lindberg RL, Kappos L, Leppert D, Petzold A, Giovannoni G, Kuhle J (2013) Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS ONE 8(9):e75091. doi:10.1371/journal.pone.0075091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gleichmann M, Mattson MP (2011) Neuronal calcium homeostasis and dysregulation. Antioxid Redox Signal 14(7):1261–1273. doi:10.1089/ars.2010.3386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goodall EF, Morrison KE (2006) Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment. Expert Rev Mol Med 8(11):1–22. doi:10.1017/S1462399406010854

    Article  PubMed  Google Scholar 

  • Grossman M, Elman L, McCluskey L, McMillan CT, Boller A, Powers J, Rascovsky K, Hu W, Shaw L, Irwin DJ, Lee VM, Trojanowski JQ (2014) Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis. JAMA Neurol 71(4):442–448. doi:10.1001/jamaneurol.2013.6064

    Article  PubMed  PubMed Central  Google Scholar 

  • Henkel JS, Beers DR, Zhao W, Appel SH (2009) Microglia in ALS: the good, the bad, and the resting. J Neuroimmune Pharmacol 4(4):389–398. doi:10.1007/s11481-009-9171-5

    Article  PubMed  Google Scholar 

  • Hensley K, Fedynyshyn J, Ferrell S, Floyd RA, Gordon B, Grammas P, Hamdheydari L, Mhatre M, Mou S, Pye QN, Stewart C, West M, West S, Williamson KS (2003) Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alpha-modulating cytokines in spinal cords of the G93A-SOD1 mouse model for amyotrophic lateral sclerosis. Neurobiol Dis 14(1):74–80

    Article  CAS  PubMed  Google Scholar 

  • Howland DS, Liu J, She Y, Goad B, Maragakis NJ, Kim B, Erickson J, Kulik J, De Vito L, Psaltis G, De Gennaro LJ, Cleveland DW, Rothstein JD (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci USA 99(3):1604–1609. doi:10.1073/pnas.032539299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iaccarino C, Mura ME, Esposito S, Carta F, Sanna G, Turrini F, Carri MT, Crosio C (2011) Bcl2-A1 interacts with pro-caspase-3: implications for amyotrophic lateral sclerosis. Neurobiol Dis 43(3):642–650. doi:10.1016/j.nbd.2011.05.013

    Article  CAS  PubMed  Google Scholar 

  • Islam AT, Kwak J, Jung Y, Kee Y (2014) Animal models of amyotrophic lateral sclerosis and Huntington’s disease. Genes Genomics 36(4):399–413. doi:10.1007/s13258-014-0188-7

    Article  CAS  Google Scholar 

  • Ito H (2014) Basophilic inclusions and neuronal intermediate filament inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Neuropathology 34(6):589–595

    Article  CAS  PubMed  Google Scholar 

  • Jain MR, Ge WW, Elkabes S, Li H (2008) Amyotrophic lateral sclerosis: protein chaperone dysfunction revealed by proteomic studies of animal models. Proteomics Clin Appl 2(5):670–684. doi:10.1002/prca.200780023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joyce PI, Fratta P, Fisher EM, Acevedo-Arozena A (2011) SOD1 and TDP-43 animal models of amyotrophic lateral sclerosis: recent advances in understanding disease toward the development of clinical treatments. Mamm Genome 22(7–8):420–448. doi:10.1007/s00335-011-9339-1

    Article  CAS  PubMed  Google Scholar 

  • Julien JP (2007) ALS: astrocytes move in as deadly neighbors. Nat Neurosci 10(5):535–537. doi:10.1038/nn0507-535

    Article  CAS  PubMed  Google Scholar 

  • Kabashi E, Durham HD (2006) Failure of protein quality control in amyotrophic lateral sclerosis. Biochimica et Biophysica Acta (BBA)—Mol Basis Dis 1762(11–12):1038–1050. doi:10.1016/j.bbadis.2006.06.006

    Google Scholar 

  • Kakizawa S, Miyazaki T, Yanagihara D, Iino M, Watanabe M, Kano M (2005) Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain. Proc Natl Acad Sci USA 102(52):19180–19185. doi:10.1073/pnas.0504359103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang SH, Li Y, Fukaya M, Lorenzini I, Cleveland DW, Ostrow LW, Rothstein JD, Bergles DE (2013) Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nat Neurosci 16(5):571–579. doi:10.1038/nn.3357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato S, Hayashi H, Nakashima K, Nanba E, Kato M, Hirano A, Nakano I, Asayama K, Ohama E (1997) Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis. Am J Pathol 151(2):611–620

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kato S, Horiuchi S, Liu J, Cleveland DW, Shibata N, Nakashima K, Nagai R, Hirano A, Takikawa M, Kato M, Nakano I, Ohama E (2000) Advanced glycation endproduct-modified superoxide dismutase-1 (SOD1)-positive inclusions are common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutations and transgenic mice expressing human SOD1 with a G85R mutation. Acta Neuropathol 100(5):490–505

    Article  CAS  PubMed  Google Scholar 

  • Kawamata T, Akiyama H, Yamada T, McGeer PL (1992) Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 140(3):691–707

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91(2):461–553. doi:10.1152/physrev.00011.2010

    Article  CAS  PubMed  Google Scholar 

  • Kiaei M, Petri S, Kipiani K, Gardian G, Choi DK, Chen J, Calingasan NY, Schafer P, Muller GW, Stewart C, Hensley K, Beal MF (2006) Thalidomide and lenalidomide extend survival in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci 26(9):2467–2473. doi:10.1523/JNEUROSCI.5253-05.2006

    Article  CAS  PubMed  Google Scholar 

  • Klein SM, Behrstock S, McHugh J, Hoffmann K, Wallace K, Suzuki M, Aebischer P, Svendsen CN (2005) GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum Gene Ther 16(4):509–521. doi:10.1089/hum.2005.16.509

    Article  CAS  PubMed  Google Scholar 

  • Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 347(9013):1425–1431

    Article  CAS  PubMed  Google Scholar 

  • Lanson NA Jr, Pandey UB (2012) FUS-related proteinopathies: lessons from animal models. Brain Res 1462:44–60. doi:10.1016/j.brainres.2012.01.039

    Article  CAS  PubMed  Google Scholar 

  • Lasiene J, Yamanaka K (2011) Glial cells in amyotrophic lateral sclerosis. Neurol Res Int 2011:718987. doi:10.1155/2011/718987

    Article  PubMed  PubMed Central  Google Scholar 

  • Lau A, Tymianski M (2010) Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch 460(2):525–542. doi:10.1007/s00424-010-0809-1

    Article  CAS  PubMed  Google Scholar 

  • Leal SS, Cardoso I, Valentine JS, Gomes CM (2013) Calcium ions promote superoxide dismutase 1 (SOD1) aggregation into non-fibrillar amyloid: a link to toxic effects of calcium overload in amyotrophic lateral sclerosis (ALS)? J Biol Chem 288(35):25219–25228. doi:10.1074/jbc.M113.470740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee S, Kim HJ (2015) Prion-like mechanism in amyotrophic lateral sclerosis: are protein aggregates the key? Exp Neurobiol 24(1):1–7. doi:10.5607/en.2015.24.1.1

    Article  PubMed  Google Scholar 

  • Lee HJ, Kim KS, Ahn J, Bae HM, Lim I, Kim SU (2014) Human motor neurons generated from neural stem cells delay clinical onset and prolong life in ALS mouse model. PLoS ONE 9(5):e97518. doi:10.1371/journal.pone.0097518

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lehman N (2009) The ubiquitin proteasome system in neuropathology. Acta Neuropathol 118(3):329–347. doi:10.1007/s00401-009-0560-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P, Gan Y, Mao L, Leak R, Chen J, Hu X (2014) The critical roles of immune cells in acute brain injuries. In: The critical roles of immune cells in acute brain injuries. Springer. doi:10.1007/978-1-4614-8915-3_2

    Google Scholar 

  • Liem RK, Messing A (2009) Dysfunctions of neuronal and glial intermediate filaments in disease. J Clin Invest 119(7):1814–1824. doi:10.1172/JCI38003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330(9):613–622. doi:10.1056/NEJM199403033300907

    Article  CAS  PubMed  Google Scholar 

  • Llorens J (2013) Toxic neurofilamentous axonopathies—accumulation of neurofilaments and axonal degeneration. J Intern Med 273(5):478–489. doi:10.1111/joim.12030

    Article  CAS  PubMed  Google Scholar 

  • Logroscino G, Traynor BJ, Hardiman O, Chio A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E, Eurals (2010) Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81(4):385–390. doi:10.1136/jnnp.2009.183525

    Article  PubMed  Google Scholar 

  • Ludemann N, Clement A, Hans VH, Leschik J, Behl C, Brandt R (2005) O-glycosylation of the tail domain of neurofilament protein M in human neurons and in spinal cord tissue of a rat model of amyotrophic lateral sclerosis (ALS). J Biol Chem 280(36):31648–31658. doi:10.1074/jbc.M504395200

    Article  PubMed  CAS  Google Scholar 

  • Mackenzie IR, Rademakers R, Neumann M (2010) TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 9(10):995–1007. doi:10.1016/S1474-4422(10)70195-2

    Article  CAS  PubMed  Google Scholar 

  • Mandrekar-Colucci S, Landreth GE (2010) Microglia and inflammation in Alzheimer’s disease. CNS Neurol Disord Drug Targets 9(2):156–167

    Article  CAS  PubMed  Google Scholar 

  • Marangi G, Traynor BJ (2015) Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges. Brain Res 1607:75–93. doi:10.1016/j.brainres.2014.10.009

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto S, Goto S, Kusaka H, Imai T, Murakami N, Hashizume Y, Okazaki H, Hirano A (1993) Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: a comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and Werdnig-Hoffmann disease. J Neurol Sci 115(2):208–213

    Article  CAS  PubMed  Google Scholar 

  • Mazzini L, Gelati M, Profico DC, Sgaravizzi G, Projetti Pensi M, Muzi G, Ricciolini C, Rota Nodari L, Carletti S, Giorgi C, Spera C, Domenico F, Bersano E, Petruzzelli F, Cisari C, Maglione A, Sarnelli MF, Stecco A, Querin G, Masiero S, Cantello R, Ferrari D, Zalfa C, Binda E, Visioli A, Trombetta D, Novelli A, Torres B, Bernardini L, Carriero A, Prandi P, Servo S, Cerino A, Cima V, Gaiani A, Nasuelli N, Massara M, Glass J, Soraru G, Boulis NM, Vescovi AL (2015) Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med 13(1):17. doi:10.1186/s12967-014-0371-2

    Article  PubMed  PubMed Central  Google Scholar 

  • McGeer PL, McGeer EG (2002) Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve 26(4):459–470. doi:10.1002/mus.10191

    Article  CAS  PubMed  Google Scholar 

  • McGoldrick P, Joyce PI, Fisher EM, Greensmith L (2013) Rodent models of amyotrophic lateral sclerosis. Biochim Biophys Acta 1832(9):1421–1436. doi:10.1016/j.bbadis.2013.03.012

    Article  CAS  PubMed  Google Scholar 

  • Meldrum B, Garthwaite J (1990) Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 11(9):379–387

    Article  CAS  PubMed  Google Scholar 

  • Mezzapesa DM, D’Errico E, Tortelli R, Distaso E, Cortese R, Tursi M, Federico F, Zoccolella S, Logroscino G, Dicuonzo F, Simone IL (2013) Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis. PLoS ONE 8(11):e80748. doi:10.1371/journal.pone.0080748

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mitrecic D, Nicaise C, Gajovic S, Pochet R (2010) Distribution, differentiation, and survival of intravenously administered neural stem cells in a rat model of amyotrophic lateral sclerosis. Cell Transplant 19(5):537–548. doi:10.3727/096368910X498269

    Article  PubMed  Google Scholar 

  • Moisse K, Strong MJ (2006) Innate immunity in amyotrophic lateral sclerosis. Biochim Biophys Acta 1762(11–12):1083–1093. doi:10.1016/j.bbadis.2006.03.001

    Article  CAS  PubMed  Google Scholar 

  • Muzio L, Martino G, Furlan R (2007) Multifaceted aspects of inflammation in multiple sclerosis: the role of microglia. J Neuroimmunol 191(1–2):39–44. doi:10.1016/j.jneuroim.2007.09.016

    Article  CAS  PubMed  Google Scholar 

  • Nakamura Y, Si QS, Kataoka K (1999) Lipopolysaccharide-induced microglial activation in culture: temporal profiles of morphological change and release of cytokines and nitric oxide. Neurosci Res 35(2):95–100

    Article  CAS  PubMed  Google Scholar 

  • Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21(6):736–745. doi:10.1016/j.bbi.2007.03.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133. doi:10.1126/science.1134108

    Article  CAS  PubMed  Google Scholar 

  • Niebroj-Dobosz I, Dziewulska D, Kwiecinski H (2004) Oxidative damage to proteins in the spinal cord in amyotrophic lateral sclerosis (ALS). Folia Neuropathol 42(3):151–156

    CAS  PubMed  Google Scholar 

  • Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7(9):710–723. doi:10.1038/nrn1971

    Article  CAS  PubMed  Google Scholar 

  • Patel P, Kriz J, Gravel M, Soucy G, Bareil C, Gravel C, Julien JP (2014) Adeno-associated virus-mediated delivery of a recombinant single-chain antibody against misfolded superoxide dismutase for treatment of amyotrophic lateral sclerosis. Mol Ther 22(3):498–510. doi:10.1038/mt.2013.239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pehar M, Cassina P, Vargas MR, Castellanos R, Viera L, Beckman JS, Estevez AG, Barbeito L (2004) Astrocytic production of nerve growth factor in motor neuron apoptosis: implications for amyotrophic lateral sclerosis. J Neurochem 89(2):464–473. doi:10.1111/j.1471-4159.2004.02357.x

    Article  CAS  PubMed  Google Scholar 

  • Piao YS, Wakabayashi K, Kakita A, Yamada M, Hayashi S, Morita T, Ikuta F, Oyanagi K, Takahashi H (2003) Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. Brain Pathol 13(1):10–22

    Article  PubMed  Google Scholar 

  • Ransohoff RM, Kivisakk P, Kidd G (2003) Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 3(7):569–581. doi:10.1038/nri1130

    Article  CAS  PubMed  Google Scholar 

  • Rao SD, Weiss JH (2004) Excitotoxic and oxidative cross-talk between motor neurons and glia in ALS pathogenesis. Trends Neurosci 27(1):17–23

    Article  CAS  PubMed  Google Scholar 

  • Rizzo F, Riboldi G, Salani S, Nizzardo M, Simone C, Corti S, Hedlund E (2014) Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell Mol Life Sci 71(6):999–1015. doi:10.1007/s00018-013-1480-4

    Article  CAS  PubMed  Google Scholar 

  • Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A (2007) Neuroinflammation in Alzheimer’s disease and Parkinson’s disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82:235–246. doi:10.1016/S0074-7742(07)82012-5

    Article  CAS  PubMed  Google Scholar 

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62. doi:10.1038/362059a0

    Article  CAS  PubMed  Google Scholar 

  • Rossi FH, Franco MC, Estevez AG (2013) Pathophysiology of Amyotrophic Lateral Sclerosis. In: Estévez AG (ed) Current Advances in Amyotrophic Lateral Sclerosis. ISBN: 978-953-51-1195-5. doi:10.5772/56562. http://www.intechopen.com/books/current-advances-in-amyotrophic-lateral-sclerosis/pathophysiology-ofamyotrophic-lateral-sclerosis

    Google Scholar 

  • Rothstein JD (2009) Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol 65(Suppl 1):S3–S9. doi:10.1002/ana.21543

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326(22):1464–1468. doi:10.1056/NEJM199205283262204

    Article  CAS  PubMed  Google Scholar 

  • Schiffer D, Cordera S, Cavalla P, Migheli A (1996) Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J Neurol Sci 139:27–33

    Article  PubMed  Google Scholar 

  • Scotter E, Chen H-J, Shaw C (2015) TDP-43 proteinopathy and ALS: insights into disease mechanisms and therapeutic targets. Neurotherapeutics 12(2):352–363. doi:10.1007/s13311-015-0338-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw BF, Valentine JS (2007) How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of the protein? Trends Biochem Sci 32(2):78–85

    Article  CAS  PubMed  Google Scholar 

  • Shinder GA, Lacourse M-C, Minotti S, Durham HD (2001) Mutant Cu/Zn-superoxide dismutase proteins have altered solubility and interact with heat shock/stress proteins in models of amyotrophic lateral sclerosis. J Biol Chem 276(16):12791–12796. doi:10.1074/jbc.M010759200

    Article  CAS  PubMed  Google Scholar 

  • Shobha K, Alladi PA, Nalini A, Sathyaprabha TN, Raju TR (2010) Exposure to CSF from sporadic amyotrophic lateral sclerosis patients induces morphological transformation of astroglia and enhances GFAP and S100beta expression. Neurosci Lett 473(1):56–61. doi:10.1016/j.neulet.2010.02.022

    Article  CAS  PubMed  Google Scholar 

  • Smethurst P, Sidle KC, Hardy J (2014) Invited review: prion-like mechanisms of transactive response DNA binding protein of 43 kDa (TDP-43) in amyotrophic lateral sclerosis (ALS). Neuropathol Appl Neurobiol. doi:10.1111/nan.12206

    Google Scholar 

  • Smith D, Uryu K, Saatman K, Trojanowski J, McIntosh T (2003) Protein accumulation in traumatic brain injury. NeuroMol Med 4(1–2):59–72. doi:10.1385/NMM:4:1-2:59

    Article  CAS  Google Scholar 

  • Soriani MH, Desnuelle C (2009) Epidemiology of amyotrophic lateral sclerosis. Rev Neurol 165(8–9):627–640. doi:10.1016/j.neurol.2009.04.004 (Paris)

    Article  PubMed  Google Scholar 

  • Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319(5870):1668–1672. doi:10.1126/science.1154584

    Article  CAS  PubMed  Google Scholar 

  • Stamer K, Vogel R, Thies E, Mandelkow E, Mandelkow E-M (2002) Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J Cell Biol 156(6):1051–1063. doi:10.1083/jcb.200108057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Streit WJ, Mrak RE, Griffin WST (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflamm 1(1):14

    Article  CAS  Google Scholar 

  • Takahashi T, Yagishita S, Amano N, Yamaoka K, Kamei T (1997) Amyotrophic lateral sclerosis with numerous axonal spheroids in the corticospinal tract and massive degeneration of the cortex. Acta Neuropathol 94(3):294–299

    Article  CAS  PubMed  Google Scholar 

  • Tovar YRLB, Ramirez-Jarquin UN, Lazo-Gomez R, Tapia R (2014) Trophic factors as modulators of motor neuron physiology and survival: implications for ALS therapy. Front Cell Neurosci 8:61. doi:10.3389/fncel.2014.00061

    Google Scholar 

  • Tracey KJ (2002) The inflammatory reflex. Nature 420(6917):853–859. doi:10.1038/nature01321

    Article  CAS  PubMed  Google Scholar 

  • Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62(3):405–496. doi:10.1124/pr.109.002451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Troost D, Sillevis Smitt PA, de Jong JM, Swaab DF (1992) Neurofilament and glial alterations in the cerebral cortex in amyotrophic lateral sclerosis. Acta Neuropathol 84(6):664–673

    Article  CAS  PubMed  Google Scholar 

  • Tummala H, Jung C, Tiwari A, Higgins CMJ, Hayward LJ, Xu Z (2005) Inhibition of chaperone activity is a shared property of several Cu, Zn-Superoxide dismutase mutants that cause amyotrophic lateral sclerosis. J Biol Chem 280(18):17725–17731. doi:10.1074/jbc.M501705200

    Article  CAS  PubMed  Google Scholar 

  • Turner MR, Cagnin A, Turkheimer FE, Miller CC, Shaw CE, Brooks DJ, Leigh PN, Banati RB (2004) Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis 15(3):601–609. doi:10.1016/j.nbd.2003.12.012

    Article  CAS  PubMed  Google Scholar 

  • Upadhyay A, Amanullah A, Chhangani D, Mishra R, Mishra A (2015a) Selective multifaceted E3 ubiquitin ligases barricade extreme defense: Potential therapeutic targets for neurodegeneration and ageing. Ageing Res Rev. doi:10.1016/j.arr.2015.07.009

    PubMed  Google Scholar 

  • Upadhyay A, Amanullah A, Chhangani D, Mishra R, Prasad A, Mishra A (2015b) Mahogunin ring finger-1 (MGRN1), a multifaceted ubiquitin ligase: recent unraveling of neurobiological mechanisms. Mol Neurobiol. doi:10.1007/s12035-015-9379-8

    Google Scholar 

  • Urushitani M, Kurisu J, Tsukita K, Takahashi R (2002) Proteasomal inhibition by misfolded mutant superoxide dismutase 1 induces selective motor neuron death in familial amyotrophic lateral sclerosis. J Neurochem 83(5):1030–1042

    Article  CAS  PubMed  Google Scholar 

  • Van Damme P, Robberecht W (2014) Developments in treatments for amyotrophic lateral sclerosis via intracerebroventricular or intrathecal delivery. Expert Opin Investig Drugs 23(7):955–963. doi:10.1517/13543784.2014.912275

    Article  PubMed  CAS  Google Scholar 

  • Van Den Bosch L, Van Damme P, Bogaert E, Robberecht W (2006) The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta 1762(11–12):1068–1082. doi:10.1016/j.bbadis.2006.05.002

    Article  CAS  Google Scholar 

  • Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323(5918):1208–1211. doi:10.1126/science.1165942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe M, Dykes-Hoberg M, Cizewski Culotta V, Price DL, Wong PC, Rothstein JD (2001) Histological evidence of protein aggregation in mutant SOD1 transgenic mice and in amyotrophic lateral sclerosis neural tissues. Neurobiol Dis 8(6):933–941. doi:10.1006/nbdi.2001.0443

    Article  CAS  PubMed  Google Scholar 

  • Weydt P, Möller T (2005) Neuroinflammation in the pathogenesis of amyotrophic lateral sclerosis. NeuroReport 16(6):527–531

    Article  PubMed  Google Scholar 

  • Wijesekera LC, Leigh PN (2009) Amyotrophic lateral sclerosis. Orphanet J Rare Dis 4:3. doi:10.1186/1750-1172-4-3

    Article  PubMed  PubMed Central  Google Scholar 

  • Wong NK, He BP, Strong MJ (2000) Characterization of neuronal intermediate filament protein expression in cervical spinal motor neurons in sporadic amyotrophic lateral sclerosis (ALS). J Neuropathol Exp Neurol 59(11):972–982

    Article  CAS  PubMed  Google Scholar 

  • Yang W, Sopper MM, Leystra-Lantz C, Strong MJ (2003) Microtubule-associated tau protein positive neuronal and glial inclusions in ALS. Neurology 61(12):1766–1773

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Gozen O, Watkins A, Lorenzini I, Lepore A, Gao Y, Vidensky S, Brennan J, Poulsen D, Won Park J, Li Jeon N, Robinson MB, Rothstein JD (2009) Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron 61(6):880–894. doi:10.1016/j.neuron.2009.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshihara T, Ishigaki S, Yamamoto M, Liang Y, Niwa J, Takeuchi H, Doyu M, Sobue G (2002) Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 80(1):158–167

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Schuff N, Woolley SC, Chiang GC, Boreta L, Laxamana J, Katz JS, Weiner MW (2011) Progression of white matter degeneration in amyotrophic lateral sclerosis: a diffusion tensor imaging study. Amyotroph Lateral Scler 12(6):421–429. doi:10.3109/17482968.2011.593036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao W, Varghese M, Yemul S, Pan Y, Cheng A, Marano P, Hassan S, Vempati P, Chen F, Qian X, Pasinetti GM (2011) Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1alpha) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis. Mol Neurodegener 6(1):51. doi:10.1186/1750-1326-6-51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou JY, Afjehi-Sadat L, Asress S, Duong DM, Cudkowicz M, Glass JD, Peng J (2010) Galectin-3 is a candidate biomarker for amyotrophic lateral sclerosis: discovery by a proteomics approach. J Proteome Res 9(10):5133–5141. doi:10.1021/pr100409r

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM (2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417(6884):74–78. doi:10.1038/417074a

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Department of Biotechnology, Government of India. AM was supported by Ramalinganswami Fellowship (BT/RLF/Reentry/11/2010) and Innovative Young Biotechnologist Award (IYBA) scheme (BT/06/IYBA/2012) from the Department of Biotechnology, Government of India. AU and VJ were supported by a research fellowship from the Council of Scientific and Industrial Research-University Grants Commission (CSIR-UGC), Government of India. The authors would like to thank Mr. Bharat Pareek for his technical assistance and the entire lab management during the manuscript preparation. We apologize to various authors whose work could not be included due to space limitations.

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  1. Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, 342011, Rajasthan, India

    Arun Upadhyay, Ayeman Amanullah, Vibhuti Joshi, Ribhav Mishra & Amit Mishra

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  1. Molecular and Cellular Neuroscience, National Brain Research Centre, Gurgaon, Delhi, India

    Nihar Jana

  2. Molecular and Cellular Neuroscience, National Brain Research Centre, Gurgaon, Delhi, India

    Anirban Basu

  3. National Brain Research Centre, National Research Professor, National Brain Research Centre, Gurgaon, Delhi, India

    Prakash Narain Tandon

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Upadhyay, A., Amanullah, A., Joshi, V., Mishra, R., Mishra, A. (2016). Molecular and Cellular Insights: Neuroinflammation and Amyotrophic Lateral Sclerosis. In: Jana, N., Basu, A., Tandon, P. (eds) Inflammation: the Common Link in Brain Pathologies. Springer, Singapore. https://doi.org/10.1007/978-981-10-1711-7_8

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