Amyloid beta-protein: physiological and toxicological role- Biophysical inquiry into ptotein aggregation and amyloid diseases.

The amyloid ?-protein (A?) is the major component of neuritic plaques that are the prominent feature of Alzheimer's disease (AD). A? is a 39-42 amino acid peptide that can be accumulated extracellularly and derives from multiple proteolytic cleavage of a large transmembrane precursor, the amyloid precursor protein (APP). It is widely accepted that AD syndrome can be correlated to either altered APP expression or proteolytic processing, or to changes in A? stability and following aggregation.Although neuronal degeneration occurs near the amyloid plaques, some studies have suggested that intermediates such as protofibrils and A?-derived diffusible ligands (ADDLs) or simple oligomers are involved in AD pathogenesis. Toxic properties for aggregates of different size have been investigated and support the possibility that different pathways leading to degeneration could be undertaken. Considering the important role played by A? in AD, different strategies have been developed to target A? molecule in potential therapeutic treatments.