Dietary supplementation with 3-deaza adenosine, N-acetyl cysteine, and S-adenosyl methionine provide neuroprotection against multiple consequences of vitamin deficiency and oxidative challenge: relevance to age-related neurodegeneration.
Folate deprivation induces neurotoxicity that is potentiated by additional nutritional and genetic deficiencies including vitamin E and apolipoprotein E deficiency. These deficiencies collectively induce oxidative damage, cognitive impairment, and compensatory alteration in glutathione generation. Treatment with agents that regulate distinct portions of the methionine cycle, including the S-adenosyl homocysteine hydrolase inhibitor, 3-deaza adenosine, the methyl donor S-adenosyl methionine, and the antioxidant N-acetyl cysteine, provide neuroprotection against various aspects of neurotoxicity in normal and apolipoprotein E-deficient mice and in cultured neuronal cells deprived of dietary folate and vitamin E and subjected to iron overload. Here it is demonstrated that simultaneous treatment with these agents provide superior neuroprotection by alleviating individual and overlapping neurotoxic consequences. These findings support combinatorial treatments with agents that compensate for differential insults in age-related neurodegenerative disorders.
Tchantchou
Flaubert
F
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Graves
Michael
M
Ortiz
Daniela
D
Rogers
Eugene
E
Shea
Thomas B
TB
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D045744:Cell Line, Tumor; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005494:Folic Acid Deficiency / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D005981:Glutathione Synthase / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014372:Tubercidin / Q000008:administration & dosage / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000517:prevention & control*
D001057:Apolipoproteins E; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; C018258:3-deazaadenosine; D012436:S-Adenosylmethionine; D005981:Glutathione Synthase; D005978:Glutathione; D014372:Tubercidin; D000111:Acetylcysteine