The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders.
This review focuses on the biochemical and clinical aspects of methylation in neuropsychiatric disorders and the clinical potential of their treatment with ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.
Bottiglieri
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Metabolic Disease Center, Baylor Research Institute, Dallas, Texas.
Hyland
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Reynolds
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EH
D015526:AIDS Dementia Complex / Q000188:drug therapy; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000188:drug therapy; D003704:Dementia / Q000188:drug therapy; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000188:drug therapy; D008727:Methotrexate / Q000009:adverse effects; D008745:Methylation; D009103:Multiple Sclerosis / Q000188:drug therapy; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013118:Spinal Cord Diseases / Q000188:drug therapy
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D012436:S-Adenosylmethionine; D008727:Methotrexate