ORC ID ">
  • Users Online: 1878
  • Home
  • Print this page
  • Email this page
REVIEW
Year : 2018  |  Volume : 13  |  Issue : 7  |  Page : 1136-1144

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


1 Bio@SNS Laboratory, Scuola Normale Superiore, Pisa; Department of Pharmacy, University of Pisa, Pisa, Italy
2 Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy

Correspondence Address:
Emanuela Colla
Bio@SNS Laboratory, Scuola Normale Superiore, Pisa
Italy
Login to access the Email id

Source of Support: 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, Conflict of Interest: None


DOI: 10.4103/1673-5374.235013

Rights and Permissions

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.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed6163    
    Printed32    
    Emailed0    
    PDF Downloaded1112    
    Comments [Add]    
    Cited by others 29    

Recommend this journal