Proteasome augmentation for Alzheimer's disease

Enhancing neuronal proteasomal activity using peptide analogs could help treat Alzheimer's disease. In hippocampal samples from the NIH NeuroBioBank, proteasomal activity was decreased in both early- and late-stage Alzheimer's patients compared with healthy controls, and proteasome function was inversely correlated with levels of APP and soluble Aβ42.

In a drosophila model of Alzheimer's expressing human APP and BACE1, genetic overexpression of a proteasome subunit prevented deficits in associative learning and circadian rhythm compared with AD flies not overexpressing the proteasome subunit. In transgenic mice expressing mutant human APP, overexpression of a neuronal proteasome subunit decreased spatial memory deficits and increased survival compared with no proteasome overexpression. ...