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 i...
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doaj-17ce9a01557644f583801c47bb052ce82020-11-25T00:17:17ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-01-0120114110.3390/ijms20010141ijms20010141Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and PathologyFrancesca Longhena0Gaia Faustini1Maria Grazia Spillantini2Arianna Bellucci3Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, ItalyDivision of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, ItalyDepartment of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UKDivision of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, ItalyAlpha-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.http://www.mdpi.com/1422-0067/20/1/141α-synucleinsynaptic proteinsconformational plasticitysynucleinopathiesinteractome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francesca Longhena Gaia Faustini Maria Grazia Spillantini Arianna Bellucci |
spellingShingle |
Francesca Longhena Gaia Faustini Maria Grazia Spillantini Arianna Bellucci Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology International Journal of Molecular Sciences α-synuclein synaptic proteins conformational plasticity synucleinopathies interactome |
author_facet |
Francesca Longhena Gaia Faustini Maria Grazia Spillantini Arianna Bellucci |
author_sort |
Francesca Longhena |
title |
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_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_sort |
living in promiscuity: the multiple partners of alpha-synuclein at the synapse in physiology and pathology |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-01-01 |
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. |
topic |
α-synuclein synaptic proteins conformational plasticity synucleinopathies interactome |
url |
http://www.mdpi.com/1422-0067/20/1/141 |
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