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Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of the upper and lower motor neurons. Despite the increasing effort in understanding the etiopathology of ALS, it still remains an obscure disease, and no therapies are currently available to h...
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/PMC8951432/ https://www.ncbi.nlm.nih.gov/pubmed/35323676 http://dx.doi.org/10.3390/metabo12030233 |
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author | Candelise, Niccolò Salvatori, Illari Scaricamazza, Silvia Nesci, Valentina Zenuni, Henri Ferri, Alberto Valle, Cristiana |
author_facet | Candelise, Niccolò Salvatori, Illari Scaricamazza, Silvia Nesci, Valentina Zenuni, Henri Ferri, Alberto Valle, Cristiana |
author_sort | Candelise, Niccolò |
collection | PubMed |
description | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of the upper and lower motor neurons. Despite the increasing effort in understanding the etiopathology of ALS, it still remains an obscure disease, and no therapies are currently available to halt its progression. Following the discovery of the first gene associated with familial forms of ALS, Cu–Zn superoxide dismutase, it appeared evident that mitochondria were key elements in the onset of the pathology. However, as more and more ALS-related genes were discovered, the attention shifted from mitochondria impairment to other biological functions such as protein aggregation and RNA metabolism. In recent years, mitochondria have again earned central, mechanistic roles in the pathology, due to accumulating evidence of their derangement in ALS animal models and patients, often resulting in the dysregulation of the energetic metabolism. In this review, we first provide an update of the last lustrum on the molecular mechanisms by which the most well-known ALS-related proteins affect mitochondrial functions and cellular bioenergetics. Next, we focus on evidence gathered from human specimens and advance the concept of a cellular-specific mitochondrial “metabolic threshold”, which may appear pivotal in ALS pathogenesis. |
format | Online Article Text |
id | pubmed-8951432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89514322022-03-26 Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship Candelise, Niccolò Salvatori, Illari Scaricamazza, Silvia Nesci, Valentina Zenuni, Henri Ferri, Alberto Valle, Cristiana Metabolites Review Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of the upper and lower motor neurons. Despite the increasing effort in understanding the etiopathology of ALS, it still remains an obscure disease, and no therapies are currently available to halt its progression. Following the discovery of the first gene associated with familial forms of ALS, Cu–Zn superoxide dismutase, it appeared evident that mitochondria were key elements in the onset of the pathology. However, as more and more ALS-related genes were discovered, the attention shifted from mitochondria impairment to other biological functions such as protein aggregation and RNA metabolism. In recent years, mitochondria have again earned central, mechanistic roles in the pathology, due to accumulating evidence of their derangement in ALS animal models and patients, often resulting in the dysregulation of the energetic metabolism. In this review, we first provide an update of the last lustrum on the molecular mechanisms by which the most well-known ALS-related proteins affect mitochondrial functions and cellular bioenergetics. Next, we focus on evidence gathered from human specimens and advance the concept of a cellular-specific mitochondrial “metabolic threshold”, which may appear pivotal in ALS pathogenesis. MDPI 2022-03-09 /pmc/articles/PMC8951432/ /pubmed/35323676 http://dx.doi.org/10.3390/metabo12030233 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 Candelise, Niccolò Salvatori, Illari Scaricamazza, Silvia Nesci, Valentina Zenuni, Henri Ferri, Alberto Valle, Cristiana Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship |
title | Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship |
title_full | Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship |
title_fullStr | Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship |
title_full_unstemmed | Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship |
title_short | Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship |
title_sort | mechanistic insights of mitochondrial dysfunction in amyotrophic lateral sclerosis: an update on a lasting relationship |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951432/ https://www.ncbi.nlm.nih.gov/pubmed/35323676 http://dx.doi.org/10.3390/metabo12030233 |
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