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 Alzheimers 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.
Keywords: β-amyloid, Alzheimer's disease, aggregation inhibitors
Current Medicinal Chemistry
Title: Beta Amyloid Aggregation Inhibitors: Small Molecules as Candidate Drugs for Therapy of Alzheimers Disease
Volume: 17 Issue: 27
Author(s): F. Re, C. Airoldi, C. Zona, M. Masserini, B. La Ferla, N. Quattrocchi and F. Nicotra
Affiliation:
Keywords: β-amyloid, Alzheimer's disease, aggregation inhibitors
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 Alzheimers 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.
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Cite this article as:
Re F., Airoldi C., Zona C., Masserini M., Ferla B. La, Quattrocchi N. and Nicotra F., Beta Amyloid Aggregation Inhibitors: Small Molecules as Candidate Drugs for Therapy of Alzheimers Disease, Current Medicinal Chemistry 2010; 17 (27) . https://dx.doi.org/10.2174/092986710791959729
DOI https://dx.doi.org/10.2174/092986710791959729 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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