Protection mechanisms against Abeta42 aggregation.

It is widely accepted that Abeta42 aggregation is a central event in the pathogenesis of Alzheimer's disease. Abeta42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death and eventually dementia. There are a number of physiological molecules that can protect Abeta42 from aggregation. Promoting such protective molecules and mechanisms against Abeta42 aggregation may be a novel direction in AD drug discovery. One of the most striking protective molecules is none other than Abeta40, which inhibits Abeta42 aggregation in a specific and dosage dependent manner. Abeta40 is a critical, built-in mechanism against Abeta42 aggregation. A number of other molecules and mechanisms also inhibit Abeta42 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.