Amyloid beta: structure, biology and structure-based therapeutic development

Amyloid beta peptide (A beta) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by beta- and gamma-secretases. A beta accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of A beta are and by what mechanism A beta causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease. In this paper, we review the structures, biological functions, and neurotoxicity role of A beta. We also discuss the potential receptors that interact with A beta and mediate A beta intake, clearance, and metabolism. Additionally, we summarize the therapeutic developments and recent advances of different strategies for treating Alzheimer's disease. Finally, we will report on the progress in searching for novel, potentially effective agents as well as selected promising strategies for the treatment of Alzheimer's disease. These prospects include agents acting on A beta, its receptors and tau protein, such as small molecules, vaccines and antibodies against A beta; inhibitors or modulators of beta- and beta-secretase; A beta-degrading proteases; tau protein inhibitors and vaccines; amyloid dyes and microRNAs.