Centrality of Early Synaptopathy in Parkinson's Disease.

Abstract:

: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 stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the 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.

journal_name

Front Neurol

journal_title

Frontiers in neurology

authors

Imbriani P,Schirinzi T,Meringolo M,Mercuri NB,Pisani A

doi

10.3389/fneur.2018.00103

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

103

issn

1664-2295

journal_volume

9

pub_type

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