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Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is one of several chronic neurodegenerative conditions in which mitochondrial abnormalities are posited to contribute to disease progression. Therapeutic options targeting mitochondria include enhancing metabolism, suppressing reactive oxygen production and disrupting m...

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Detalles Bibliográficos
Autor principal: Dorn, Gerald W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136928/
https://www.ncbi.nlm.nih.gov/pubmed/37190097
http://dx.doi.org/10.3390/cells12081188
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author Dorn, Gerald W.
author_facet Dorn, Gerald W.
author_sort Dorn, Gerald W.
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description Amyotrophic lateral sclerosis is one of several chronic neurodegenerative conditions in which mitochondrial abnormalities are posited to contribute to disease progression. Therapeutic options targeting mitochondria include enhancing metabolism, suppressing reactive oxygen production and disrupting mitochondria-mediated programmed cell death pathways. Herein is reviewed mechanistic evidence supporting a meaningful pathophysiological role for the constellation of abnormal mitochondrial fusion, fission and transport, collectively designated mitochondrial dysdynamism, in ALS. Following this is a discussion on preclinical studies in ALS mice that seemingly validate the idea that normalizing mitochondrial dynamism can delay ALS by interrupting a vicious cycle of mitochondrial degeneration, leading to neuronal die-back and death. Finally, the relative benefits of suppressing mitochondrial fusion vs. enhancing mitochondrial fusion in ALS are speculated upon, and the paper concludes with the prediction that the two approaches could be additive or synergistic, although a side-by-side comparative trial may be challenging to perform.
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spelling pubmed-101369282023-04-28 Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis Dorn, Gerald W. Cells Review Amyotrophic lateral sclerosis is one of several chronic neurodegenerative conditions in which mitochondrial abnormalities are posited to contribute to disease progression. Therapeutic options targeting mitochondria include enhancing metabolism, suppressing reactive oxygen production and disrupting mitochondria-mediated programmed cell death pathways. Herein is reviewed mechanistic evidence supporting a meaningful pathophysiological role for the constellation of abnormal mitochondrial fusion, fission and transport, collectively designated mitochondrial dysdynamism, in ALS. Following this is a discussion on preclinical studies in ALS mice that seemingly validate the idea that normalizing mitochondrial dynamism can delay ALS by interrupting a vicious cycle of mitochondrial degeneration, leading to neuronal die-back and death. Finally, the relative benefits of suppressing mitochondrial fusion vs. enhancing mitochondrial fusion in ALS are speculated upon, and the paper concludes with the prediction that the two approaches could be additive or synergistic, although a side-by-side comparative trial may be challenging to perform. MDPI 2023-04-19 /pmc/articles/PMC10136928/ /pubmed/37190097 http://dx.doi.org/10.3390/cells12081188 Text en © 2023 by the author. 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
Dorn, Gerald W.
Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis
title Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis
title_full Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis
title_fullStr Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis
title_full_unstemmed Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis
title_short Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis
title_sort reversing dysdynamism to interrupt mitochondrial degeneration in amyotrophic lateral sclerosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136928/
https://www.ncbi.nlm.nih.gov/pubmed/37190097
http://dx.doi.org/10.3390/cells12081188
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