Cargando…
Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection
Modern pharmacotherapy of neurodegenerative diseases is predominantly symptomatic and does not allow vicious circles causing disease development to break. Protein misfolding is considered the most important pathogenetic factor of neurodegenerative diseases. Physiological mechanisms related to the fu...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820882/ https://www.ncbi.nlm.nih.gov/pubmed/36614266 http://dx.doi.org/10.3390/ijms24010823 |
_version_ | 1784865566214848512 |
---|---|
author | Voronin, Mikhail V. Abramova, Elena V. Verbovaya, Ekaterina R. Vakhitova, Yulia V. Seredenin, Sergei B. |
author_facet | Voronin, Mikhail V. Abramova, Elena V. Verbovaya, Ekaterina R. Vakhitova, Yulia V. Seredenin, Sergei B. |
author_sort | Voronin, Mikhail V. |
collection | PubMed |
description | Modern pharmacotherapy of neurodegenerative diseases is predominantly symptomatic and does not allow vicious circles causing disease development to break. Protein misfolding is considered the most important pathogenetic factor of neurodegenerative diseases. Physiological mechanisms related to the function of chaperones, which contribute to the restoration of native conformation of functionally important proteins, evolved evolutionarily. These mechanisms can be considered promising for pharmacological regulation. Therefore, the aim of this review was to analyze the mechanisms of endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) in the pathogenesis of neurodegenerative diseases. Data on BiP and Sigma1R chaperones in clinical and experimental studies of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are presented. The possibility of neuroprotective effect dependent on Sigma1R ligand activation in these diseases is also demonstrated. The interaction between Sigma1R and BiP-associated signaling in the neuroprotection is discussed. The performed analysis suggests the feasibility of pharmacological regulation of chaperone function, possibility of ligand activation of Sigma1R in order to achieve a neuroprotective effect, and the need for further studies of the conjugation of cellular mechanisms controlled by Sigma1R and BiP chaperones. |
format | Online Article Text |
id | pubmed-9820882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98208822023-01-07 Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection Voronin, Mikhail V. Abramova, Elena V. Verbovaya, Ekaterina R. Vakhitova, Yulia V. Seredenin, Sergei B. Int J Mol Sci Review Modern pharmacotherapy of neurodegenerative diseases is predominantly symptomatic and does not allow vicious circles causing disease development to break. Protein misfolding is considered the most important pathogenetic factor of neurodegenerative diseases. Physiological mechanisms related to the function of chaperones, which contribute to the restoration of native conformation of functionally important proteins, evolved evolutionarily. These mechanisms can be considered promising for pharmacological regulation. Therefore, the aim of this review was to analyze the mechanisms of endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) in the pathogenesis of neurodegenerative diseases. Data on BiP and Sigma1R chaperones in clinical and experimental studies of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are presented. The possibility of neuroprotective effect dependent on Sigma1R ligand activation in these diseases is also demonstrated. The interaction between Sigma1R and BiP-associated signaling in the neuroprotection is discussed. The performed analysis suggests the feasibility of pharmacological regulation of chaperone function, possibility of ligand activation of Sigma1R in order to achieve a neuroprotective effect, and the need for further studies of the conjugation of cellular mechanisms controlled by Sigma1R and BiP chaperones. MDPI 2023-01-03 /pmc/articles/PMC9820882/ /pubmed/36614266 http://dx.doi.org/10.3390/ijms24010823 Text en © 2023 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 Voronin, Mikhail V. Abramova, Elena V. Verbovaya, Ekaterina R. Vakhitova, Yulia V. Seredenin, Sergei B. Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection |
title | Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection |
title_full | Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection |
title_fullStr | Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection |
title_full_unstemmed | Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection |
title_short | Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection |
title_sort | chaperone-dependent mechanisms as a pharmacological target for neuroprotection |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820882/ https://www.ncbi.nlm.nih.gov/pubmed/36614266 http://dx.doi.org/10.3390/ijms24010823 |
work_keys_str_mv | AT voroninmikhailv chaperonedependentmechanismsasapharmacologicaltargetforneuroprotection AT abramovaelenav chaperonedependentmechanismsasapharmacologicaltargetforneuroprotection AT verbovayaekaterinar chaperonedependentmechanismsasapharmacologicaltargetforneuroprotection AT vakhitovayuliav chaperonedependentmechanismsasapharmacologicaltargetforneuroprotection AT seredeninsergeib chaperonedependentmechanismsasapharmacologicaltargetforneuroprotection |