It is widely accepted that Aβ42 aggregation is a central event in the pathogenesis of Alzheimer's disease. Aβ42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death and eventually dementia. There are a number of physiological molecules that can protect Aβ42 from aggregation. Promoting such protective molecules and mechanisms against Aβ42 aggregation may be a novel direction in AD drug discovery. One of the most striking protective molecules is none other than Aβ40, which inhibits Aβ42 aggregation in a specific and dosage dependent manner. Aβ40 is a critical, built-in mechanism against Aβ42 aggregation. A number of other molecules and mechanisms also inhibit Aβ42 aggregation, such as heat shock proteins, L-PGDS, heme and methionine oxidation. The relevance of these protective mechanisms to AD pathogenesis and intervention is discussed.
Keywords: Amyloid-β peptide (Aβ), Alzheimer’s disease (AD), protection, Aβ42 aggregation, Aβ40, NMR, heat shock protein, L-PGDS, heme, methionine oxidation, neprilysin (NEP), insulin degrading enzyme (IDE), matrix metalloprotease (MMP), ADAM10, SIRT1.
