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

Biomolecules

Marco Emanuele²  Evelina Chieregatti¹ 

[1] Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genoa, Italy; E-Mail

关键词: alpha-synuclein;    exo/endocytosis;    calcium entry;    non-cell autonomous;    lipid microdomains;   

DOI  :  10.3390/biom5020865

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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