中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (7): 1136-1144.doi: 10.4103/1673-5374.235013

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

α-突触核蛋白聚集体的亚细胞定位及其与膜的相互作用

  

  • 收稿日期:2018-05-09 出版日期:2018-07-15 发布日期:2018-07-15

Subcellular localization of alpha-synuclein aggregates and their interaction with membranes

Fabiana Miraglia1, 2, Alessio Ricci1, Lucia Rota1, Emanuela Colla1   

  1. 1 Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy;
    2 Department of Pharmacy, University of Pisa, Pisa, Italy
  • Received:2018-05-09 Online:2018-07-15 Published:2018-07-15
  • Contact: Emanuela Colla, Ph.D.,emanuela.colla@sns.it.
  • Supported by:

    This work has been supported by the Italian Ministry of University and Research (MIUR) through the Career Reintegration grant scheme (RLM Program for Young Researcher) and from Scuola Normale Superiore.

摘要:

orcid:0000-0002-4755-7450(Emanuela Colla)

Abstract:

For more than a decade numerous evidence has been reported on the mechanisms of toxicity of α-synuclein (αS) oligomers and aggregates in α-synucleinopathies. These species were thought to form freely in the cytoplasm but recent reports of αS multimer conformations when bound to synaptic vesicles in physiological conditions, have raised the question about where αS aggregation initiates. In this review we focus on recent literature regarding the impact on membrane binding and subcellular localization of αS toxic species to understand how regular cellular function of αS contributes to pathology. Notably αS has been reported to mainly associate with specific membranes in neurons such as those of synaptic vesicles, ER/Golgi and the mitochondria, while toxic species of αS have been shown to inhibit, among others, neurotransmission, protein trafficking and mitochondrial function. Strategies interfering with αS membrane binding have shown to improve αS-driven toxicity in worms and in mice. Thus, a selective membrane binding that would result in a specific subcellular localization could be the key to understand how aggregation and pathology evolves, pointing out to αS functions that are primarily affected before onset of irreversible damage.

Key words: alpha-synuclein, oligomers, aggregates, subcellular localization, membranes binding, Parkinson’s disease, neurodegeneration, alpha-synucleinopathie