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The Neurochaperonopathies: Anomalies of the Chaperone System with Pathogenic Effects in Neurodegenerative and Neuromuscular Disorders

Authors :
Federica Scalia
Alessandra Maria Vitale
Radha Santonocito
Everly Conway de Macario
Alberto J. L. Macario
Francesco Cappello
Source :
Applied Sciences, Vol 11, Iss 3, p 898 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic NCPs are linked to pathogenic variants of chaperone genes encoding, for example, the small Hsp, Hsp10, Hsp40, Hsp60, and CCT-BBS (chaperonin-containing TCP-1- Bardet–Biedl syndrome) chaperones. Instead, the acquired NCPs are associated with malfunctional chaperones, such as Hsp70, Hsp90, and VCP/p97 with aberrant post-translational modifications. Awareness of the chaperonopathies as the underlying primary or secondary causes of disease will improve diagnosis and patient management and open the possibility of investigating and developing chaperonotherapy, namely treatment with the abnormal chaperone as the main target. Positive chaperonotherapy would apply in chaperonopathies by defect, i.e., chaperone insufficiency, and consist of chaperone replacement or boosting, whereas negative chaperonotherapy would be pertinent when a chaperone actively participates in the initiation and progression of the disease and must be blocked and eliminated.

Details

Language :
English
ISSN :
20763417
Volume :
11
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Applied Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.1df9e999e3541fabd0a66748b46d66a
Document Type :
article
Full Text :
https://doi.org/10.3390/app11030898