> Some case-control studies claimed that carriage of ALDH2x2 allele was a risk of late-onset Alzheimer's disease independent of the apolipoprotein E gene (the odds for LOAD in carriers of ALDH2x2 allele almost twice that of non-carriers). Moreover, ALDH gene, protein expression and activity are substantially decreased in the substantia nigra of Parkinson's disease patients. These reports are in line with findings implementing toxic lipid oxidation-derived aldehydes in these diseases and in neurodegeneration in general.
> The ALDH2-/- mice display age-related memory deficits in various tasks, as well as endothelial dysfunction, brain atrophy, and other Alzheimer's disease-associated pathologies, including marked increases in lipid peroxidation products, amyloid-beta, p-tau and activated caspases. These behavioral and biochemical Alzheimer's disease-like deficits were efficiently ameliorated when the ALDH2-/- mice were treated with isotope-reinforced, deuterated polyunsaturated fatty acids (D-PUFA).
D-PUFA is interesting (and being investigated for use in other diseases, e.g. Huntington's) but it's just addressing the proximal cause of the neurodegeneration (= the build-up of peroxidation products in the brain) rather than the mechanism by which those products are produced.
I'm much more curious to know whether introduction of exogenous ALDH2 into the body (perhaps above wild-type expressed levels of ALDH2) might be neuroprotective/prophylactic against neurodegenerative disease. As far as I can search, though, nobody's ever even extracted+purified an ALDH2 enzymatic solution, let alone tested it for such effects.
Specifically these quotes:
> Some case-control studies claimed that carriage of ALDH2x2 allele was a risk of late-onset Alzheimer's disease independent of the apolipoprotein E gene (the odds for LOAD in carriers of ALDH2x2 allele almost twice that of non-carriers). Moreover, ALDH gene, protein expression and activity are substantially decreased in the substantia nigra of Parkinson's disease patients. These reports are in line with findings implementing toxic lipid oxidation-derived aldehydes in these diseases and in neurodegeneration in general.
> The ALDH2-/- mice display age-related memory deficits in various tasks, as well as endothelial dysfunction, brain atrophy, and other Alzheimer's disease-associated pathologies, including marked increases in lipid peroxidation products, amyloid-beta, p-tau and activated caspases. These behavioral and biochemical Alzheimer's disease-like deficits were efficiently ameliorated when the ALDH2-/- mice were treated with isotope-reinforced, deuterated polyunsaturated fatty acids (D-PUFA).
D-PUFA is interesting (and being investigated for use in other diseases, e.g. Huntington's) but it's just addressing the proximal cause of the neurodegeneration (= the build-up of peroxidation products in the brain) rather than the mechanism by which those products are produced.
I'm much more curious to know whether introduction of exogenous ALDH2 into the body (perhaps above wild-type expressed levels of ALDH2) might be neuroprotective/prophylactic against neurodegenerative disease. As far as I can search, though, nobody's ever even extracted+purified an ALDH2 enzymatic solution, let alone tested it for such effects.