Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med. 2001;344:1688–700.
Rosen DR. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;364:362.
Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43. Cell. 2009;136:1001–4.
Renton AE, Chio A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17:17–23.
Haidet-Phillips AM, et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol. 2011;29:824–8.
Meyer K, et al. Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. Proc Natl Acad Sci U S A. 2014;111:829–32.
Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007;10:608–14.
Nagai M, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci. 2007;10:615–22.
Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell. 2008;3:637–48.
Marchetto MC, et al. Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell. 2008;3:649–57.
Papadeas ST, Kraig SE, O'Banion C, Lepore AC, Maragakis NJ. Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neuron degeneration in vivo. Proc Natl Acad Sci U S A. 2011;108:17803–8.
Yamanaka K, et al. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc Natl Acad Sci U S A. 2008;105:7594–9.
Tong J, et al. Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats. EMBO J. 2013;32:1917–26.
Rossi S, Cozzolino M, Carri MT. Old versus new mechanisms in the pathogenesis of ALS. Brain Pathol. 2016;26:276–86.
Foran E, Trotti D. Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid Redox Signal. 2009;11:1587–602.
Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol. 1995;38:73–84.
Lin CL, et al. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron. 1998;20:589–602.
Howland DS, et al. Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A. 2002;99:1604–9.
Raoul C, et al. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron. 2002;35:1067–83.
Barbeito LH, et al. A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev. 2004;47:263–74.
Endo F, et al. Astrocyte-derived TGF-β1 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells. Cell Rep. 2015;11:592–604.
Tripathi P, et al. Reactive astrocytes promote ALS-like degeneration and intracellular protein aggregation in human motor neurons by disrupting autophagy through TGF-β1. Stem cell reports. 2017;9:667–80.
Phatnani, H.P., et al. Intricate interplay between astrocytes and motor neurons in ALS. Proc Natl Acad Sci U S A 110, E756–EE765 (2013).
Brambilla L, et al. Disruption of the astrocytic TNFR1-GDNF axis accelerates motor neuron degeneration and disease progression in amyotrophic lateral sclerosis. Hum Mol Genet. 2016;25:3080–95.
Das MM, Svendsen CN. Astrocytes show reduced support of motor neurons with aging that is accelerated in a rodent model of ALS. Neurobiol Aging. 2015;36:1130–9.
Van Den Bosch L, et al. Effects of vascular endothelial growth factor (VEGF) on motor neuron degeneration. Neurobiol Dis. 2004;17:21–8.
Oosthuyse B, et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet. 2001;28:131–8.
Bogaert E, et al. VEGF protects motor neurons against excitotoxicity by upregulation of GluR2. Neurobiol Aging. 2010;31:2185–91.
Gros-Louis F, et al. Absence of mutations in the hypoxia response element of VEGF in ALS. Muscle Nerve. 2003;28:774–5.
Llado J, Tolosa L, Olmos G. Cellular and molecular mechanisms involved in the neuroprotective effects of VEGF on motoneurons. Front Cell Neurosci. 2013;7:181.
Mishra PS, et al. Astroglia acquires a toxic neuroinflammatory role in response to the cerebrospinal fluid from amyotrophic lateral sclerosis patients. J Neuroinflammation. 2016;13:212.
Re DB, et al. Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron. 2014;81:1001–8.
Hitomi J, et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008;135:1311–23.
Wiedemann FR, Manfredi G, Mawrin C, Beal MF, Schon EA. Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem. 2002;80:616–25.
Hirano A, et al. Fine structural study of neurofibrillary changes in a family with amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 1984;43:471–80.
Sasaki S, Horie Y, Iwata M. Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis. Acta Neuropathol. 2007;114:633–9.
Tan W, et al. Small peptides against the mutant SOD1/Bcl-2 toxic mitochondrial complex restore mitochondrial function and cell viability in mutant SOD1-mediated ALS. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013;33:11588–98.
Nicaise C, Mitrecic D, Falnikar A, Lepore AC. Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury. World J Stem Cells. 2015;7:380–98.
Tannenbaum SE, et al. Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications. PLoS One. 2012;7:e35325.
Prathalingam N, et al. Production and validation of a good manufacturing practice grade human fibroblast line for supporting human embryonic stem cell derivation and culture. Stem Cell Res Ther. 2012;3:12.
Izrael M, et al. Human oligodendrocytes derived from embryonic stem cells: effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci. 2007;34:310–23.
Scholze AR, Foo LC, Mulinyawe S, Barres BA. BMP signaling in astrocytes downregulates EGFR to modulate survival and maturation. PLoS One. 2014;9:e110668.
Alfei L, et al. Hyaluronate receptor CD44 is expressed by astrocytes in the adult chicken and in astrocyte cell precursors in early development of the chick spinal cord. Eur J Histochem. 1999;43:29–38.
Piao C, et al. Thrombin decreases expression of the glutamate transporter GLAST and inhibits glutamate uptake in primary cortical astrocytes via the Rho kinase pathway. Exp Neurol. 2015;273:288–300.
Baba H, et al. GFAP gene expression during development of astrocyte. Dev Neurosci. 1997;19:49–57.
Hubbard JA, Hsu MS, Seldin MM, Binder DK. Expression of the astrocyte water channel Aquaporin-4 in the mouse brain. ASN Neuro. 2015;7(5).
Gropp M, et al. Standardization of the teratoma assay for analysis of pluripotency of human ES cells and biosafety of their differentiated progeny. PLoS One. 2012;7:e45532.
Kawahara K, et al. Selective blockade of astrocytic glutamate transporter GLT-1 with dihydrokainate prevents neuronal death during ouabain treatment of astrocyte/neuron cocultures. Glia. 2002;40:337–49.
Straten G, Eschweiler GW, Maetzler W, Laske C, Leyhe T. Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer's disease and normal controls. J Alzheimers Dis. 2009;18:331–7.
Li G, et al. Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects. PLoS One. 2009;4:e5424.
Gurney ME, et al. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science. 1994;264:1772–5.
Writing G, Edaravone ALSSG. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2017;16:505–12.
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994;330:585–91.
Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet. 1996;347:1425–31.
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). The Cochrane database of systematic reviews. 2012;14(3):CD001447.
Petrov D, Mansfield C, Moussy A, Hermine O. ALS clinical trials review: 20 years of failure. are we any closer to registering a new treatment? Front Aging Neurosci. 2017;9:68.
Izrael M, Slutsky S, Itskovitz-Eldor J. & Revel M. Astrocytes in Pathogenesis of Neurodegenerative Diseases and Potential: Translation into Clinic. InTechOpen: Astrocyte—Physiology and Pathology, ISBN 978–953–51-5760-1 (Mar 2018).
Lee J, et al. Astrocytes and microglia as non-cell autonomous players in the pathogenesis of ALS. Experimental neurobiology. 2016;25:233–40.
Do-Ha D, Buskila Y, Ooi L. Impairments in motor neurons, interneurons and astrocytes contribute to hyperexcitability in ALS: underlying mechanisms and paths to therapy. Mol Neurobiol. 2017;55(2):1410–18.
Storkebaum E, Lambrechts D, Carmeliet P. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. BioEssays. 2004;26:943–54.
Krakora D, et al. Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model. Molecular therapy : the journal of the American Society of Gene Therapy. 2013;21(8):1602–10.
Ramamohan PY, et al. Cerebrospinal fluid from amyotrophic lateral sclerosis patients causes fragmentation of the Golgi apparatus in the neonatal rat spinal cord. Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases. 2007;8:79–82.
Deepa P, et al. Down regulation of trophic factors in neonatal rat spinal cord after administration of cerebrospinal fluid from sporadic amyotrophic lateral sclerosis patients. J Neural Transm. 2011;118:531–8.
Shruthi S, et al. Brain-derived neurotrophic factor facilitates functional recovery from ALS-cerebral spinal fluid-induced neurodegenerative changes in the NSC-34 motor neuron cell line. Neurodegener Dis. 2017;17:44–58.
Rosito M, Deflorio C, Limatola C, Trettel F. CXCL16 orchestrates adenosine A3 receptor and MCP-1/CCL2 activity to protect neurons from excitotoxic cell death in the CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012;32:3154–63.
Christopherson KS, et al. Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell. 2005;120:421–33.
Tyzack GE, et al. Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression. Nat Commun. 2014;5:4294.
Hafner A, et al. Neuroprotective role of gamma-enolase in microglia in a mouse model of Alzheimer's disease is regulated by cathepsin X. Aging Cell. 2013;12:604–14.
Morisaki Y, et al. Selective expression of Osteopontin in ALS-resistant motor neurons is a critical determinant of late phase neurodegeneration mediated by matrix metalloproteinase-9. Sci Rep. 2016;6:27354.
Kaplan A, et al. Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration. Neuron. 2014;81:333–48.
Wright MC, et al. Novel roles for osteopontin and clusterin in peripheral motor and sensory axon regeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2014;34:1689–700.
Meller R, et al. Neuroprotection by osteopontin in stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2005;25:217–25.
Gardner J, Ghorpade A. Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix metalloproteinases in the central nervous system. J Neurosci Res. 2003;74:801–6.
Israelson A, et al. Macrophage migration inhibitory factor as a chaperone inhibiting accumulation of misfolded SOD1. Neuron. 2015;86:218–32.
Cordero-Llana O, et al. Clusterin secreted by astrocytes enhances neuronal differentiation from human neural precursor cells. Cell Death Differ. 2011;18:907–13.
Winkler C, Yao S. The midkine family of growth factors: diverse roles in nervous system formation and maintenance. Br J Pharmacol. 2014;171:905–12.
Philips T, Rothstein JD. Rodent models of amyotrophic lateral sclerosis. Current protocols in pharmacology. 2015;69:5 67 61-65 67 21.
Collins MA, An J, Hood BL, Conrads TP, Bowser RP. Label-free LC-MS/MS proteomic analysis of cerebrospinal fluid identifies protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis. J Proteome Res. 2015;14:4486–501.
Tarasiuk J, Kulakowska A, Drozdowski W, Kornhuber J, Lewczuk P. CSF markers in amyotrophic lateral sclerosis. J Neural Transm. 2012;119:747–57.
Gao L, Zhou S, Cai H, Gong Z, Zang D. VEGF levels in CSF and serum in mild ALS patients. J Neurol Sci. 2014;346(1-2):216–20.
Varghese AM, et al. Chitotriosidase—a putative biomarker for sporadic amyotrophic lateral sclerosis. Clin Proteomics. 2013;10:19.
Przyborski SA. Differentiation of human embryonic stem cells after transplantation in immune-deficient mice. Stem Cells. 2005;23:1242–50.
Andrews PW, et al. Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochem Soc Trans. 2005;33:1526–30.
Lee AS, et al. Effects of cell number on teratoma formation by human embryonic stem cells. Cell Cycle. 2009;8:2608–12.
Prokhorova TA, et al. Teratoma formation by human embryonic stem cells is site dependent and enhanced by the presence of Matrigel. Stem Cells Dev. 2009;18:47–54.
Ramot Y, et al. Compact MRI for the detection of teratoma development following intrathecal human embryonic stem cell injection in NOD-SCID mice. Neurotoxicology. 2017;59:27–32.
Priest CA, Manley NC, Denham J, Wirth ED 3rd, Lebkowski JS. Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury. 2015;10(8):939–58.
Staff NP, et al. Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS. Neurology. 2016;87:2230–4.
Oh KW, et al. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. 2015;4:590–7.
Tian C, et al. Autologous bone marrow mesenchymal stem cell therapy in the subacute stage of traumatic brain injury by lumbar puncture. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2013;11:176–81.
Wang S, et al. Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury. Brain Res. 2013;1532:76–84.
Roybon L, et al. Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes. Cell Rep. 2013;4:1035–48.
Gupta K, Chandran S, Hardingham GE. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration. Br J Clin Pharmacol. 2013;75:907–18.
Petrou P, et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA neurology. 2016;73:337–44.
Glass JD, et al. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 2012;30:1144–51.
Mazzini L, et al. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med. 2015;13:17.
Kondo T, et al. Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice. Stem cell reports. 2014;3:242–9.
Nizzardo M, et al. iPSC-derived LewisX+CXCR4+β1-integrin+ neural stem cells improve the amyotrophic lateral sclerosis phenotype by preserving motor neurons and muscle innervation in human and rodent models. Hum Mol Genet. 2016;25:3152–63.
Scott S, et al. Design, power, and interpretation of studies in the standard murine model of ALS. Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases. 2008;9:4–15.