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and in Table 12 for Study 6

Abbreviations AAV: adeno-associated virus AD: Alzheimers disease Akt: protein kinase B ALS: amyotrophic lateral sclerosis ALS2: alsin rho guanine nucleotide exchange factor AMPA: -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ANG: angiogenin APAF-1: apoptotic protease activating factor 1 APE1: apurinic/apyrimidinic endonuclease 1 APP: amyloid precursor protein ATP: adenosine triphosphate BBB: blood-brain barrier bFGF: basic fibroblast growth factor BV-2: cellosaurus cell line BV-2 C9orf72: C9 open reading frame 72 cAMP: cyclic AMP CBT: corticobulbar tract CD4+: cluster of differentiation 4 CD8+: cluster of differentiation 8 CGN: cerebellar granule cells ChAT: choline acetyl transferase CK: cytokine CNS: central nervous system CREB: cAMP-response element-binding protein CST: corticospinal tract DAMP: damage-associated molecular pattern DNA: deoxyribonucleic acid EAE : experimental autoimmune encephalomyelitis ERK: extracellular signal-regulated kinase FAK1: focal adhesion kinase 1 fALS: familial ALS FOXO3: forkhead box O3 FUS: fused in sarcoma GCL: granule cell layer GDNF: glial-derived neurotrophic factor GLP: glucagon-like peptide-1 GLP-1R: glucagon-like peptide-1 receptor GSK-3: glycogen synthase kinase-3 HD: Huntingtons disease HNE: 4-hydroxy-2-nonenal HSP: heat shock proteins HUVEC: human umbilical vein endothelial cells IGF-1: insulin-like growth factor-1 IGF-1R: insulin-like growth factor-1 receptor IGF-2: insulin-like growth factor-2 IGFBP-1: insulin-like growth factor binding protein-1 IL: interleukin iNOS: inducible nitric oxide synthase LMN: lower motor neuron LPS: lipopolysaccharide LTB4: leukotriene B4 MAG: myelin-associated glycoprotein MOG: myelin oligodendrocyte glycoprotein MBP: myelin basic protein MDC: monodansylcadaverine mHtt: mutant Huntingtin protein MND: motor neuron disease MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MS: multiple sclerosis MSC: mesenchymal stromal cells mTOR: mammalian target of Rapamycin NDD: neurodegenerative disorders NF-B: nuclear factor kappa light chain enhancer of activated B cells NMDA: N-methyl D-aspartate NO: nitric oxide NR2B: N-methyl D-aspartate receptor subtype 2B 3-NT: 3-nitrotyrosine 3-oxoG: 8-oxo-deoxyguanosine ODC: oligodendrocyte cells OPC: oligodendrocyte progenitor cells OS: oxidative stress PARP-1: poly ADP ribose polymerase-1 PC12: pheochromocytoma cell 12 PD: Parkinsons disease PDK1: 3-phosphoinositide-dependent protein kinase 1 PEG: polyethylene glycol PGE: prostaglandin E PI3K: phosphoinositide 3-kinase PKA: protein kinase A PLP: pyridoxal phosphate Pro-OL: pro-oligodendroblast PS1: presenilin 1 RCT: randomized controlled trial rhIGF-1: recombinant human IGF-1 RNS: reactive nitrogen species ROS: reactive oxygen species sALS: sporadic ALS siRNA: small interference RNA SN: substantia nigra SOD: superoxide dismutase 1 Src kinase: proto-oncogene tyrosine-protein kinase TARDBP: TAR DNA-binding protein TDP-43: Tar DNA-binding protein 43 TEM: transmission electron microscopy Th1: T helper cell type 1 TLR-4: toll-like receptor-4 TNF-: tumor necrosis factor- TNF-R1: tumor necrosis factor receptor 1 Treg: regulatory T cells UMN: upper motor neuron VAPB: vesicle-associated membrane protein-associated protein B References Underwood LE, Thissen JP, Lemozy S, Ketelslegers JM, Clemmons DR (1994) Hormonal and nutritional regulation of IGF-I and its binding proteins

PMCID:PMC10328709

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The single-dose trial appeared to have slightly higher exposure compared with the other trials in the dataset (although this was not statistically significant at the p = 0.01 level), indicating that a trial factor could be present

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