Beta Amyloid Aggregation Inhibitors: Small Molecules as Candidate Drugs for Therapy of Alzheimer's Disease
Abstract:The progressive production and subsequent accumulation of β-amyloid (Aβ), a proteolytic fragment of the membrane-associated amyloid precursor protein (APP), plays a central role in Alzheimer's Disease (AD). Aβ is released in a soluble form that may be responsible for cognitive dysfunction in the early stages of the disease, then progressively forms oligomeric, multimeric and fibrillar aggregates, triggering neurodegeneration. Eventually, the aggregation and accumulation of Aβ culminates with the formation of extracellular plaques, one of the morphological hallmarks of the disease, detectable post-mortem in AD brains. In this review we report the known structural features of amyloid peptides and fibrils, and we give an overview of all small molecules that have been found to interact with Aβ aggregation. Deeper knowledge of the mechanism leading to amyloid fibrils along with their molecular structure and the molecular interactions responsible for activity of small molecules could supply useful information for the design of new AD therapeutic agents.
Document Type: Research Article
Affiliations: Department of Biotechnology and Biosciences, University of Milano Bicocca, piazza della Scienza 2, 20126, Milano, Italy.
Publication date: September 1, 2010
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