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Medical Hypotheses 2019-Aug

A diet rich in taurine, cysteine, folate, B12 and betaine may lessen risk for Alzheimer's disease by boosting brain synthesis of hydrogen sulfide.

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Mark McCarty
James O'Keefe
James DiNicolantonio

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概要

The gaseous physiological modulator hydrogen sulfide (H2S) has recently been shown to exert a variety of neuroprotective effects. In particular, the treatment of transgenic mouse models of Alzheimer's disease (AD) with agents that release H2S aids preservation of cognitive function, suppresses brain production of amyloid beta, and decreases tau phosphorylation. The possible physiological relevance of these findings is suggested by the finding that brain and plasma levels of H2S are markedly lower in AD patients than matched controls. Hence, nutraceutical strategies which boost brain synthesis or levels of H2S may have potential for prevention of AD. The chief enzyme which synthesizes H2S in brain parenchyma, cystathionine beta-synthase (CBS), employs cysteine as its rate-limiting substrate, and is allosterically activated by S-adenosylmethionine (SAM). Supplemental taurine has been shown to boost expression of this enzyme, as well as that of another H2S source, cystathionine gamma-lyase, in vascular tissue, and to enhance plasma H2S levels; in rats subjected to hemorrhagic stroke, co-administration of taurine has been shown to blunt a marked reduction in brain CBS expression. Brain levels of SAM are about half as high in AD patients as in controls, and this is thought to explain the reduction of brain H2S in these patients. These considerations suggest that supplementation with cysteine, taurine, and agents which promote methyl group availability - such as SAM, folate, vitamin B12, and betaine - may have potential for boosting brain synthesis of H2S and thereby aiding AD prevention. Indeed, most of these agents have already demonstrated utility in mouse AD models - albeit the extent to which increased H2S synthesis contributes to this protection remains unclear. Moreover, prospective epidemiology has associated low dietary or plasma levels of folate, B12, and taurine with increased dementia risk. Rodent studies suggest that effective nutraceutical strategies for boosting brain H2S synthesis may in fact have broad neuroprotective utility, possibly aiding prevention and/or control not only of AD but also Parkinson's disease and glaucoma, while diminishing the neuronal damage associated with brain trauma or stroke.

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