Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein

Biomolecules

Hazel L. Roberts²  David R. Brown¹ 

[1] Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK; E-Mail

关键词: α-synuclein;    neurodegeneration;    Parkinson’s disease;    aggregation;    toxic oligomers;    amyloid fibrils;   

DOI  :  10.3390/biom5020282

来源: mdpi

【 摘 要 】

In a number of neurological diseases including Parkinson’s disease (PD), α‑synuclein is aberrantly folded, forming abnormal oligomers, and amyloid fibrils within nerve cells. Strong evidence exists for the toxicity of increased production and aggregation of α-synuclein in vivo. The toxicity of α-synuclein is popularly attributed to the formation of “toxic oligomers”: a heterogenous and poorly characterized group of conformers that may share common molecular features. This review presents the available evidence on the properties of α-synuclein oligomers and the potential molecular mechanisms of their cellular disruption. Toxic α-synuclein oligomers may impact cells in a number of ways, including the disruption of membranes, mitochondrial depolarization, cytoskeleton changes, impairment of protein clearance pathways, and enhanced oxidative stress. We also examine the relationship between α-synuclein toxic oligomers and amyloid fibrils, in the light of recent studies that paint a more complex picture of α-synuclein toxicity. Finally, methods of studying and manipulating oligomers within cells are described.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.