Centrality of Early Synaptopathy in Parkinson’s Disease
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,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2018.00103/full |
| _version_ | 1819016723147259904 |
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| author | Paola Imbriani Paola Imbriani Tommaso Schirinzi Tommaso Schirinzi Maria Meringolo Maria Meringolo Nicola B. Mercuri Nicola B. Mercuri Antonio Pisani Antonio Pisani |
| author_facet | Paola Imbriani Paola Imbriani Tommaso Schirinzi Tommaso Schirinzi Maria Meringolo Maria Meringolo Nicola B. Mercuri Nicola B. Mercuri Antonio Pisani Antonio Pisani |
| author_sort | Paola Imbriani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T02:52:09Z |
| format | Article |
| id | doaj.art-e609feeef90c4acab3d883b48a6646a1 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-21T02:52:09Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-e609feeef90c4acab3d883b48a6646a12022-12-21T19:18:26ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-03-01910.3389/fneur.2018.00103340683Centrality of Early Synaptopathy in Parkinson’s DiseasePaola Imbriani0Paola Imbriani1Tommaso Schirinzi2Tommaso Schirinzi3Maria Meringolo4Maria Meringolo5Nicola B. Mercuri6Nicola B. Mercuri7Antonio Pisani8Antonio Pisani9Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, ItalyLaboratory of Neurophysiology and Plasticity, Fondazione Santa Lucia (IRCCS), Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, Rome, ItalyLaboratory of Neurophysiology and Plasticity, Fondazione Santa Lucia (IRCCS), Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, Rome, ItalyLaboratory of Neurophysiology and Plasticity, Fondazione Santa Lucia (IRCCS), Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, Rome, ItalyLaboratory of Neurophysiology and Plasticity, Fondazione Santa Lucia (IRCCS), Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, Rome, ItalyLaboratory of Neurophysiology and Plasticity, Fondazione Santa Lucia (IRCCS), Rome, ItalySignificant 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.http://journal.frontiersin.org/article/10.3389/fneur.2018.00103/fullParkinson’s diseasecellular mechanismssynaptopathydopamine transmissionanimal models |
| spellingShingle | Paola Imbriani Paola Imbriani Tommaso Schirinzi Tommaso Schirinzi Maria Meringolo Maria Meringolo Nicola B. Mercuri Nicola B. Mercuri Antonio Pisani Antonio Pisani Centrality of Early Synaptopathy in Parkinson’s Disease Frontiers in Neurology Parkinson’s disease cellular mechanisms synaptopathy dopamine transmission animal models |
| title | Centrality of Early Synaptopathy in Parkinson’s Disease |
| title_full | Centrality of Early Synaptopathy in Parkinson’s Disease |
| title_fullStr | Centrality of Early Synaptopathy in Parkinson’s Disease |
| title_full_unstemmed | Centrality of Early Synaptopathy in Parkinson’s Disease |
| title_short | Centrality of Early Synaptopathy in Parkinson’s Disease |
| title_sort | centrality of early synaptopathy in parkinson s disease |
| topic | Parkinson’s disease cellular mechanisms synaptopathy dopamine transmission animal models |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2018.00103/full |
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