S-adenosyl methionine: A connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer's disease.
Clinical manifestation of Alzheimer's disease may depend upon interaction among its risk factors. Apolipoprotein E-deficient mice undergo oxidative damage and cognitive impairment when deprived of folate. We demonstrate herein that these mice were depleted in the methyl donor S-adenosyl methionine (SAM), which inhibited glutathione S-transferase, since this enzyme requires methylation of oxidative species prior to glutathione-dependent reduction. Dietary supplementation with SAM alleviated neuropathology. Since SAM deficiency promotes presenilin-1 overexpression, which increases gamma-secretase expression and Abeta generation, these findings directly link nutritional deficiency and genetic risk factors, and support supplementation with SAM for Alzheimer's therapy.
Tchantchou
F
F
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, UMassLowell, One University Avenue, Lowell, MA 01854, USA.
Graves
M
M
Ortiz
D
D
Chan
A
A
Rogers
E
E
Shea
T B
TB
D000241:Adenosine / Q000031:analogs & derivatives* / Q000172:deficiency / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005001:Ethionine / Q000031:analogs & derivatives* / Q000172:deficiency / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D012307:Risk Factors; D014811:Vitamin E Deficiency
D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; C012167:S-adenosylethionine; D005982:Glutathione Transferase; D000241:Adenosine; D005001:Ethionine