Next Article in Journal
RNA-Binding Proteins: Splicing Factors and Disease
Next Article in Special Issue
Role of α- and β-Synucleins in the Axonal Pathology of Parkinson’s Disease and Related Synucleinopathies
Previous Article in Journal
Structural Biology of Bacterial RNA Polymerase
Previous Article in Special Issue
Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies
Open AccessReview

Mechanisms of Alpha-Synuclein Action on Neurotransmission: Cell-Autonomous and Non-Cell Autonomous Role

Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genoa, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Stephan N. Witt
Biomolecules 2015, 5(2), 865-892; https://doi.org/10.3390/biom5020865
Received: 16 March 2015 / Revised: 24 April 2015 / Accepted: 29 April 2015 / Published: 13 May 2015
Mutations and duplication/triplication of the alpha-synuclein (αSyn)-coding gene have been found to cause familial Parkinson’s disease (PD), while genetic polymorphisms in the region controlling the expression level and stability of αSyn have been identified as risk factors for idiopathic PD, pointing to the importance of wild-type (wt) αSyn dosage in the disease. Evidence that αSyn is present in the cerebrospinal fluid and interstitial brain tissue and that healthy neuronal grafts transplanted into PD patients often degenerate suggests that extracellularly-released αSyn plays a role in triggering the neurodegenerative process. αSyn’s role in neurotransmission has been shown in various cell culture models in which the protein was upregulated or deleted and in knock out and transgenic animal, with different results on αSyn’s effect on synaptic vesicle pool size and mobilization, αSyn being proposed as a negative or positive regulator of neurotransmitter release. In this review, we discuss the effect of αSyn on pre- and post-synaptic compartments in terms of synaptic vesicle trafficking, calcium entry and channel activity, and we focus on the process of exocytosis and internalization of αSyn and on the spreading of αSyn-driven effects due to the presence of the protein in the extracellular milieu. View Full-Text
Keywords: alpha-synuclein; exo/endocytosis; calcium entry; non-cell autonomous; lipid microdomains alpha-synuclein; exo/endocytosis; calcium entry; non-cell autonomous; lipid microdomains
Show Figures

Figure 1

MDPI and ACS Style

Emanuele, M.; Chieregatti, E. Mechanisms of Alpha-Synuclein Action on Neurotransmission: Cell-Autonomous and Non-Cell Autonomous Role. Biomolecules 2015, 5, 865-892.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Search more from Scilit
 
Search
Back to TopTop