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Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology

Alpha-synuclein (α-syn) is a small protein that, in neurons, localizes predominantly to presynaptic terminals. Due to elevated conformational plasticity, which can be affected by environmental factors, in addition to undergoing disorder-to-order transition upon interaction with different interactant...

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Autores principales: Longhena, Francesca, Faustini, Gaia, Spillantini, Maria Grazia, Bellucci, Arianna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337145/
https://www.ncbi.nlm.nih.gov/pubmed/30609739
http://dx.doi.org/10.3390/ijms20010141
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author Longhena, Francesca
Faustini, Gaia
Spillantini, Maria Grazia
Bellucci, Arianna
author_facet Longhena, Francesca
Faustini, Gaia
Spillantini, Maria Grazia
Bellucci, Arianna
author_sort Longhena, Francesca
collection PubMed
description Alpha-synuclein (α-syn) is a small protein that, in neurons, localizes predominantly to presynaptic terminals. Due to elevated conformational plasticity, which can be affected by environmental factors, in addition to undergoing disorder-to-order transition upon interaction with different interactants, α-syn is counted among the intrinsically disordered proteins (IDPs) family. As with many other IDPs, α-syn is considered a hub protein. This function is particularly relevant at synaptic sites, where α-syn is abundant and interacts with many partners, such as monoamine transporters, cytoskeletal components, lipid membranes, chaperones and synaptic vesicles (SV)-associated proteins. These protein–protein and protein–lipid membrane interactions are crucial for synaptic functional homeostasis, and alterations in α-syn can cause disruption of this complex network, and thus a failure of the synaptic machinery. Alterations of the synaptic environment or post-translational modification of α-syn can induce its misfolding, resulting in the formation of oligomers or fibrillary aggregates. These α-syn species are thought to play a pathological role in neurodegenerative disorders with α-syn deposits such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are referred to as synucleinopathies. Here, we aim at revising the complex and promiscuous role of α-syn at synaptic terminals in order to decipher whether α-syn molecular interactants may influence its conformational state, contributing to its aggregation, or whether they are just affected by it.
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spelling pubmed-63371452019-01-22 Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology Longhena, Francesca Faustini, Gaia Spillantini, Maria Grazia Bellucci, Arianna Int J Mol Sci Review Alpha-synuclein (α-syn) is a small protein that, in neurons, localizes predominantly to presynaptic terminals. Due to elevated conformational plasticity, which can be affected by environmental factors, in addition to undergoing disorder-to-order transition upon interaction with different interactants, α-syn is counted among the intrinsically disordered proteins (IDPs) family. As with many other IDPs, α-syn is considered a hub protein. This function is particularly relevant at synaptic sites, where α-syn is abundant and interacts with many partners, such as monoamine transporters, cytoskeletal components, lipid membranes, chaperones and synaptic vesicles (SV)-associated proteins. These protein–protein and protein–lipid membrane interactions are crucial for synaptic functional homeostasis, and alterations in α-syn can cause disruption of this complex network, and thus a failure of the synaptic machinery. Alterations of the synaptic environment or post-translational modification of α-syn can induce its misfolding, resulting in the formation of oligomers or fibrillary aggregates. These α-syn species are thought to play a pathological role in neurodegenerative disorders with α-syn deposits such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are referred to as synucleinopathies. Here, we aim at revising the complex and promiscuous role of α-syn at synaptic terminals in order to decipher whether α-syn molecular interactants may influence its conformational state, contributing to its aggregation, or whether they are just affected by it. MDPI 2019-01-02 /pmc/articles/PMC6337145/ /pubmed/30609739 http://dx.doi.org/10.3390/ijms20010141 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Longhena, Francesca
Faustini, Gaia
Spillantini, Maria Grazia
Bellucci, Arianna
Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology
title Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology
title_full Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology
title_fullStr Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology
title_full_unstemmed Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology
title_short Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology
title_sort living in promiscuity: the multiple partners of alpha-synuclein at the synapse in physiology and pathology
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337145/
https://www.ncbi.nlm.nih.gov/pubmed/30609739
http://dx.doi.org/10.3390/ijms20010141
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