Abstract
Lewy bodies (LBs) and Lewy neurites (LNs) in the brain constitute the main histopathological features of Parkinsons disease (PD) and dementia with Lewy bodies (DLB), and are comprised of amyloid-like fibrils composed of a small protein (∼14 kDa) named alpha-synuclein (αS). As the aggregation of αS in the brain has been implicated as a critical step in the development of the diseases, the current search for disease-modifying drugs is focused on modification of the process of αS deposition in the brain. In this article, the recent developments on the molecules that inhibit the formation of α-synuclein fibrils (fαS) as well as the oligomerization of αS are reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation of fαS, and to destabilize preformed fαS at pH 7.5 at 37°C in vitro. Although the mechanisms by which these compounds inhibit fαS formation from fαS, and destabilize preformed fαS are still unclear, they could be key molecules for the development of preventives and therapeutics for PD and other α-synucleinopathies.
Keywords: Parkinson's disease, α-synuclein fibrils, oligomer, organic compounds, thioflavin S, electron microscopy, atomic force microscopy
Current Pharmaceutical Design
Title: β-Synuclein Assembly as a Therapeutic Target of Parkinsons Disease and Related Disorders
Volume: 14 Issue: 30
Author(s): Kenjiro Ono, Mie Hirohata and Masahito Yamada
Affiliation:
Keywords: Parkinson's disease, α-synuclein fibrils, oligomer, organic compounds, thioflavin S, electron microscopy, atomic force microscopy
Abstract: Lewy bodies (LBs) and Lewy neurites (LNs) in the brain constitute the main histopathological features of Parkinsons disease (PD) and dementia with Lewy bodies (DLB), and are comprised of amyloid-like fibrils composed of a small protein (∼14 kDa) named alpha-synuclein (αS). As the aggregation of αS in the brain has been implicated as a critical step in the development of the diseases, the current search for disease-modifying drugs is focused on modification of the process of αS deposition in the brain. In this article, the recent developments on the molecules that inhibit the formation of α-synuclein fibrils (fαS) as well as the oligomerization of αS are reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation of fαS, and to destabilize preformed fαS at pH 7.5 at 37°C in vitro. Although the mechanisms by which these compounds inhibit fαS formation from fαS, and destabilize preformed fαS are still unclear, they could be key molecules for the development of preventives and therapeutics for PD and other α-synucleinopathies.
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Cite this article as:
Ono Kenjiro, Hirohata Mie and Yamada Masahito, β-Synuclein Assembly as a Therapeutic Target of Parkinsons Disease and Related Disorders, Current Pharmaceutical Design 2008; 14 (30) . https://dx.doi.org/10.2174/138161208786404191
DOI https://dx.doi.org/10.2174/138161208786404191 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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