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Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein agg...

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Autores principales: Jankovic, Milena, Novakovic, Ivana, Gamil Anwar Dawod, Phepy, Gamil Anwar Dawod, Ayman, Drinic, Aleksandra, Abdel Motaleb, Fayda I., Ducic, Sinisa, Nikolic, Dejan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469731/
https://www.ncbi.nlm.nih.gov/pubmed/34575995
http://dx.doi.org/10.3390/ijms22189832
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author Jankovic, Milena
Novakovic, Ivana
Gamil Anwar Dawod, Phepy
Gamil Anwar Dawod, Ayman
Drinic, Aleksandra
Abdel Motaleb, Fayda I.
Ducic, Sinisa
Nikolic, Dejan
author_facet Jankovic, Milena
Novakovic, Ivana
Gamil Anwar Dawod, Phepy
Gamil Anwar Dawod, Ayman
Drinic, Aleksandra
Abdel Motaleb, Fayda I.
Ducic, Sinisa
Nikolic, Dejan
author_sort Jankovic, Milena
collection PubMed
description Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly.
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spelling pubmed-84697312021-09-27 Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis Jankovic, Milena Novakovic, Ivana Gamil Anwar Dawod, Phepy Gamil Anwar Dawod, Ayman Drinic, Aleksandra Abdel Motaleb, Fayda I. Ducic, Sinisa Nikolic, Dejan Int J Mol Sci Review Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly. MDPI 2021-09-11 /pmc/articles/PMC8469731/ /pubmed/34575995 http://dx.doi.org/10.3390/ijms22189832 Text en © 2021 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
Jankovic, Milena
Novakovic, Ivana
Gamil Anwar Dawod, Phepy
Gamil Anwar Dawod, Ayman
Drinic, Aleksandra
Abdel Motaleb, Fayda I.
Ducic, Sinisa
Nikolic, Dejan
Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
title Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
title_full Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
title_fullStr Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
title_full_unstemmed Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
title_short Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
title_sort current concepts on genetic aspects of mitochondrial dysfunction in amyotrophic lateral sclerosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469731/
https://www.ncbi.nlm.nih.gov/pubmed/34575995
http://dx.doi.org/10.3390/ijms22189832
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