β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain
The inability to regulate the cellular proteome is a hallmark of aging and Alzheimer disease (AD). We identify the ketone body metabolic fuel β-hydroxybutyrate (βHB) as a regulator of protein solubility. This effect is selective for pathological proteins such as amyloid-β and we found that exogenous βHB ameliorates pathology in nematode models of amyloid-β aggregation toxicity. We also show that βHB targets neurodegeneration-related proteins among and clears them from the brain in a mouse model of Alzheimer disease. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.
The work was led by Professor John Newman of the Buck Institute for Aging in Novato CA. The paper was published in Cell Chemical Biology and can be found here:
https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(24)00459…