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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Main Authors: Salihu Mohammed, Isabella Russo, Ileana Ramazzina
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
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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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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