Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders.
Folate is a cofactor in one-carbon metabolism, during which it promotes the remethylation of homocysteine -- a cytotoxic sulfur-containing amino acid that can induce DNA strand breakage, oxidative stress and apoptosis. Dietary folate is required for normal development of the nervous system, playing important roles regulating neurogenesis and programmed cell death. Recent epidemiological and experimental studies have linked folate deficiency and resultant increased homocysteine levels with several neurodegenerative conditions, including stroke, Alzheimer's disease and Parkinson's disease. Moreover, genetic and clinical data suggest roles for folate and homocysteine in the pathogenesis of psychiatric disorders. A better understanding of the roles of folate and homocysteine in neuronal homeostasis throughout life is revealing novel approaches for preventing and treating neurological disorders.
Mattson
Mark P
MP
Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, National Institutes of health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov
Shea
Thomas B
TB
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D003866:Depressive Disorder / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D006710:Homocysteine / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism; D008745:Methylation; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism; D020521:Stroke / Q000378:metabolism
D006710:Homocysteine; D005492:Folic Acid