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Front. Neurol. | doi: 10.3389/fneur.2018.00103

Centrality of early synaptopathy in Parkinson’s disease

  • 1Department of Systems Medicine, Università degli Studi di Roma Tor Vergata, Italy
  • 2Fondazione Santa Lucia (IRCCS), Italy
  • 3Exp Neurol Lab, Fondazione Santa Lucia (IRCCS), Italy

Significant advances have been made in the understanding of the numerous mechanisms involved in Parkinson’s disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum (ER) stress and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses. In a number of experimental models, this synaptopathy has been shown to be an initial, central event in PD pathogenesis, preceding neuronal damage, thereby representing a valuable tool for testing potential disease-modifying treatments.

Keywords: Parkinson’s disease, Cellular Mechanisms, synaptopathy, Dopamine transmission, Animal Models

Received: 14 Dec 2017; Accepted: 13 Feb 2018.

Edited by:

Fabio Blandini, Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS), Italy

Reviewed by:

Jose L. Lanciego, Universidad de Navarra, Spain
Marie Therese Fuzzati-Armentero, France Parkinson, France  

Copyright: © 2018 Imbriani, Schirinzi, Mercuri and Pisani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Antonio Pisani, Università degli Studi di Roma Tor Vergata, Department of Systems Medicine, Roma, 00133, Italy, pisani@uniroma2.it