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Abbreviations 5-MTHF: 5-Methyltetrahydrofolate A: amyloid-beta ALSFRS-R: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale AD: Alzheimers disease ALDH1L2: 10-formyl-THF dehydrogenase ALS: Amyotrophic lateral sclerosis AMPK: Adenosine monophosphate-activated protein kinase ApoE: Apolipoprotein E ASD: Autism spectrum disorder APP: Amyloid precursor protein ATP: adenosine triphosphate BDNF: Brain-derived neurotrophic factor BH2: Dihydrobiopterin BH4: Tetrahydrobiopterin CBS: Cystathionine beta-synthase COMT: Catechol-O-methyl transferase C9orf72: Chromosome 9 open reading frame 72 CSF: Cerebrospinal fluid DHF: Dihydrofolate DHFR: Dihydrofolate reductase dTMP: Deoxythymidine monophosphate dUMP: Deoxyuridine monophosphate eNOS: Endothelial nitric oxide synthase ERK: Extracellular signal-regulated kinase FR: Folate receptor FR: Folate receptor alpha FOCM: Folate-mediated one-carbon metabolism GTPCH: GTP cyclohydrolase I GPx: Glutathione peroxidase GWAS: Genome-wide association study HHcy: Hyperhomocysteinemia Hcy: Homocysteine HD: Huntingtons disease HTT: Huntingtin IL-6: Interleukin-6 iNOS: Inducible nitric oxide synthase LCMT1: Leucine carboxyl methyltransferase LRKK2: Leucine-rich repeat kinase 2 MAPK: Mitogen-activated protein kinase MAT2A: Methionine adenosyltransferase 2 A MTHFD1: Methylenetetrahydrofolate dehydrogenase 1 MTHFD2: Methylenetetrahydrofolate dehydrogenase 2 MTHFD1L: Methylenetetrahydrofolate dehydrogenase 1-like MTHFR: Methylenetetrahydrofolate reductase MTR: Methionine synthase MS: Multiple sclerosis MTRR: Methionine synthase reductase NAD: Nicotinamide adenine dinucleotide NGF: Nerve growth factor NF-B: Nuclear factor kappa-light-chain-enhancer of activated B cells NMDA: N-methyl-D-aspartate NO: nitric oxide NTD: Neural tube defect OCM: one-carbon metabolism PARP: poly-ADP-ribose polymerase PD: Parkinsons disease PCFT: Proton-coupled folate transporter PINK1: PTEN-induced kinase 1 PRKN: Parkin RBR E3 ubiquitin protein ligase PS1: Presenilin 1 ROS: Reactive oxygen species RFC: Reduced folate carrier SAH: S-adenosylhomocysteine SAM: S-adenosylmethionine SHMT1: Serine hydroxymethyltransferase 1 SHMT2: Serine hydroxymethyltransferase 2 alpha SOD1: Superoxide dismutase TARDBP: TAR DNA-binding protein THF: Tetrahydrofolate TNF-: Tumor necrosis factor alpha TYMS: Thymidylate synthase References Ducker GS, Rabinowitz JD

In contrast, digoxin has a TI of only about 2, and for such drugs toxicity may be precipitated by relatively small changes in dosage regimen or the clearance of the drug from the body