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The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases
Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Proteostasis alteration is a pathogenic mechanism involved in many MNDs and is due to the excessive presence of misfolded and aggregated proteins. Protein misfolding may be the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569637/ https://www.ncbi.nlm.nih.gov/pubmed/36233058 http://dx.doi.org/10.3390/ijms231911759 |
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author | Tedesco, Barbara Ferrari, Veronica Cozzi, Marta Chierichetti, Marta Casarotto, Elena Pramaggiore, Paola Mina, Francesco Galbiati, Mariarita Rusmini, Paola Crippa, Valeria Cristofani, Riccardo Poletti, Angelo |
author_facet | Tedesco, Barbara Ferrari, Veronica Cozzi, Marta Chierichetti, Marta Casarotto, Elena Pramaggiore, Paola Mina, Francesco Galbiati, Mariarita Rusmini, Paola Crippa, Valeria Cristofani, Riccardo Poletti, Angelo |
author_sort | Tedesco, Barbara |
collection | PubMed |
description | Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Proteostasis alteration is a pathogenic mechanism involved in many MNDs and is due to the excessive presence of misfolded and aggregated proteins. Protein misfolding may be the product of gene mutations, or due to defects in the translation process, or to stress agents; all these conditions may alter the native conformation of proteins making them prone to aggregate. Alternatively, mutations in members of the protein quality control (PQC) system may determine a loss of function of the proteostasis network. This causes an impairment in the capability to handle and remove aberrant or damaged proteins. The PQC system consists of the degradative pathways, which are the autophagy and the proteasome, and a network of chaperones and co-chaperones. Among these components, Heat Shock Protein 70 represents the main factor in substrate triage to folding, refolding, or degradation, and it is assisted in this task by a subclass of the chaperone network, the small heat shock protein (sHSPs/HSPBs) family. HSPBs take part in proteostasis by bridging misfolded and aggregated proteins to the HSP70 machinery and to the degradative pathways, facilitating refolding or clearance of the potentially toxic proteins. Because of its activity against proteostasis alteration, the chaperone system plays a relevant role in the protection against proteotoxicity in MNDs. Here, we discuss the role of HSPBs in MNDs and which HSPBs may represent a valid target for therapeutic purposes. |
format | Online Article Text |
id | pubmed-9569637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95696372022-10-17 The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases Tedesco, Barbara Ferrari, Veronica Cozzi, Marta Chierichetti, Marta Casarotto, Elena Pramaggiore, Paola Mina, Francesco Galbiati, Mariarita Rusmini, Paola Crippa, Valeria Cristofani, Riccardo Poletti, Angelo Int J Mol Sci Review Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Proteostasis alteration is a pathogenic mechanism involved in many MNDs and is due to the excessive presence of misfolded and aggregated proteins. Protein misfolding may be the product of gene mutations, or due to defects in the translation process, or to stress agents; all these conditions may alter the native conformation of proteins making them prone to aggregate. Alternatively, mutations in members of the protein quality control (PQC) system may determine a loss of function of the proteostasis network. This causes an impairment in the capability to handle and remove aberrant or damaged proteins. The PQC system consists of the degradative pathways, which are the autophagy and the proteasome, and a network of chaperones and co-chaperones. Among these components, Heat Shock Protein 70 represents the main factor in substrate triage to folding, refolding, or degradation, and it is assisted in this task by a subclass of the chaperone network, the small heat shock protein (sHSPs/HSPBs) family. HSPBs take part in proteostasis by bridging misfolded and aggregated proteins to the HSP70 machinery and to the degradative pathways, facilitating refolding or clearance of the potentially toxic proteins. Because of its activity against proteostasis alteration, the chaperone system plays a relevant role in the protection against proteotoxicity in MNDs. Here, we discuss the role of HSPBs in MNDs and which HSPBs may represent a valid target for therapeutic purposes. MDPI 2022-10-04 /pmc/articles/PMC9569637/ /pubmed/36233058 http://dx.doi.org/10.3390/ijms231911759 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Tedesco, Barbara Ferrari, Veronica Cozzi, Marta Chierichetti, Marta Casarotto, Elena Pramaggiore, Paola Mina, Francesco Galbiati, Mariarita Rusmini, Paola Crippa, Valeria Cristofani, Riccardo Poletti, Angelo The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases |
title | The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases |
title_full | The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases |
title_fullStr | The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases |
title_full_unstemmed | The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases |
title_short | The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases |
title_sort | role of small heat shock proteins in protein misfolding associated motoneuron diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569637/ https://www.ncbi.nlm.nih.gov/pubmed/36233058 http://dx.doi.org/10.3390/ijms231911759 |
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