Abstract
Alpha-Synuclein is found in the neuronal cells but its native function is not well known. While α -synuclein is an intrinsically disordered protein that adopts a helical conformation upon membrane binding, numerous studies have shown that oligomeric β-forms of this protein are cytotoxic. This response to misfolded species contributes to Parkinson’s Disease etiology and symptoms. The resulting amyloid fibrils are an established diagnostic in Parkinson’s Disease. In this review, we focus on strategies that have been used to inhibit the amyloidogenesis of α -synuclein either by stabilizing the native state, or by redirecting the pathway to less toxic aggregates. Small molecules such as polyphenols, peptides as well as large proteins have proven effective at protecting cells against the cytotoxicity of α-synuclein. These strategies may lead to the development of therapeutic agents that could prove useful in combating this disease.
Keywords: Amyloidogenesis, antibodies, Parkinson’s Disease, polyphenol, proteins, α-synuclein.
Graphical Abstract
Current Neuropharmacology
Title:Modulating the Amyloidogenesis of α-Synuclein
Volume: 14 Issue: 3
Author(s): Kalkena Sivanesam and Niels H. Andersen
Affiliation:
Keywords: Amyloidogenesis, antibodies, Parkinson’s Disease, polyphenol, proteins, α-synuclein.
Abstract: Alpha-Synuclein is found in the neuronal cells but its native function is not well known. While α -synuclein is an intrinsically disordered protein that adopts a helical conformation upon membrane binding, numerous studies have shown that oligomeric β-forms of this protein are cytotoxic. This response to misfolded species contributes to Parkinson’s Disease etiology and symptoms. The resulting amyloid fibrils are an established diagnostic in Parkinson’s Disease. In this review, we focus on strategies that have been used to inhibit the amyloidogenesis of α -synuclein either by stabilizing the native state, or by redirecting the pathway to less toxic aggregates. Small molecules such as polyphenols, peptides as well as large proteins have proven effective at protecting cells against the cytotoxicity of α-synuclein. These strategies may lead to the development of therapeutic agents that could prove useful in combating this disease.
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Cite this article as:
Sivanesam Kalkena and Andersen H. Niels, Modulating the Amyloidogenesis of α-Synuclein, Current Neuropharmacology 2016; 14 (3) . https://dx.doi.org/10.2174/1570159X13666151030103153
DOI https://dx.doi.org/10.2174/1570159X13666151030103153 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |
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