Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease
A proteostasis network represents a sophisticated cellular system that controls the whole process which leads to properly folded functional proteins. The imbalance of proteostasis determines a quantitative increase in misfolded proteins prone to aggregation and elicits the onset of different disease...
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MDPI AG
2023-08-01
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Online Access: | https://www.mdpi.com/1422-0067/24/17/13370 |
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author | Salihu Mohammed Isabella Russo Ileana Ramazzina |
author_facet | Salihu Mohammed Isabella Russo Ileana Ramazzina |
author_sort | Salihu Mohammed |
collection | DOAJ |
description | A proteostasis network represents a sophisticated cellular system that controls the whole process which leads to properly folded functional proteins. The imbalance of proteostasis determines a quantitative increase in misfolded proteins prone to aggregation and elicits the onset of different diseases. Among these, Parkinson’s Disease (PD) is a progressive brain disorder characterized by motor and non-motor signs. In PD pathogenesis, alpha-Synuclein (α-Syn) loses its native structure, triggering a polymerization cascade that leads to the formation of toxic inclusions, the PD hallmark. Because molecular chaperones represent a “cellular arsenal” to counteract protein misfolding and aggregation, the modulation of their expression represents a compelling PD therapeutic strategy. This review will discuss evidence concerning the effects of natural and synthetic small molecules in counteracting α-Syn aggregation process and related toxicity, in different in vitro and in vivo PD models. Firstly, the role of small molecules that modulate the function(s) of chaperones will be highlighted. Then, attention will be paid to small molecules that interfere with different steps of the protein-aggregation process. This overview would stimulate in-depth research on already-known small molecules or the development of new ones, with the aim of developing drugs that are able to modify the progression of the disease. |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T23:21:49Z |
publishDate | 2023-08-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-b62e564db17e4aabaa13f94512bcbfb42023-11-19T08:16:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171337010.3390/ijms241713370Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s DiseaseSalihu Mohammed0Isabella Russo1Ileana Ramazzina2Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Via Europa 11, 25123 Brescia, ItalyDepartment of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, ItalyA proteostasis network represents a sophisticated cellular system that controls the whole process which leads to properly folded functional proteins. The imbalance of proteostasis determines a quantitative increase in misfolded proteins prone to aggregation and elicits the onset of different diseases. Among these, Parkinson’s Disease (PD) is a progressive brain disorder characterized by motor and non-motor signs. In PD pathogenesis, alpha-Synuclein (α-Syn) loses its native structure, triggering a polymerization cascade that leads to the formation of toxic inclusions, the PD hallmark. Because molecular chaperones represent a “cellular arsenal” to counteract protein misfolding and aggregation, the modulation of their expression represents a compelling PD therapeutic strategy. This review will discuss evidence concerning the effects of natural and synthetic small molecules in counteracting α-Syn aggregation process and related toxicity, in different in vitro and in vivo PD models. Firstly, the role of small molecules that modulate the function(s) of chaperones will be highlighted. Then, attention will be paid to small molecules that interfere with different steps of the protein-aggregation process. This overview would stimulate in-depth research on already-known small molecules or the development of new ones, with the aim of developing drugs that are able to modify the progression of the disease.https://www.mdpi.com/1422-0067/24/17/13370proteostasismolecular chaperonesα-Synucleinsmall moleculesParkinson’s disease |
spellingShingle | Salihu Mohammed Isabella Russo Ileana Ramazzina Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease International Journal of Molecular Sciences proteostasis molecular chaperones α-Synuclein small molecules Parkinson’s disease |
title | Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease |
title_full | Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease |
title_fullStr | Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease |
title_full_unstemmed | Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease |
title_short | Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson’s Disease |
title_sort | uncovering the role of natural and synthetic small molecules in counteracting the burden of α synuclein aggregates and related toxicity in different models of parkinson s disease |
topic | proteostasis molecular chaperones α-Synuclein small molecules Parkinson’s disease |
url | https://www.mdpi.com/1422-0067/24/17/13370 |
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