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Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis

Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive and terminal neurodegenerative disorder. Mitochondrial dysfunction, imbalance of cellular bioenergetics, electron chain transportation and calcium homeostasis are deeply associated with the progression of this disease. Impaired mitocho...

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Autores principales: Dhasmana, Swati, Dhasmana, Anupam, Kotnala, Sudhir, Mangtani, Varsha, Narula, Acharan S., Haque, Shafiul, Jaggi, Meena, Yallapu, Murali M., Chauhan, Subhash C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286590/
https://www.ncbi.nlm.nih.gov/pubmed/36111770
http://dx.doi.org/10.2174/1570159X20666220915092703
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author Dhasmana, Swati
Dhasmana, Anupam
Kotnala, Sudhir
Mangtani, Varsha
Narula, Acharan S.
Haque, Shafiul
Jaggi, Meena
Yallapu, Murali M.
Chauhan, Subhash C.
author_facet Dhasmana, Swati
Dhasmana, Anupam
Kotnala, Sudhir
Mangtani, Varsha
Narula, Acharan S.
Haque, Shafiul
Jaggi, Meena
Yallapu, Murali M.
Chauhan, Subhash C.
author_sort Dhasmana, Swati
collection PubMed
description Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive and terminal neurodegenerative disorder. Mitochondrial dysfunction, imbalance of cellular bioenergetics, electron chain transportation and calcium homeostasis are deeply associated with the progression of this disease. Impaired mitochondrial functions are crucial in rapid neurodegeneration. The mitochondria of ALS patients are associated with deregulated Ca(2+) homeostasis and elevated levels of reactive oxygen species (ROS), leading to oxidative stress. Overload of mitochondrial calcium and ROS production leads to glutamate-receptor mediated neurotoxicity. This implies mitochondria are an attractive therapeutic target. Objective: The aim of this review is to brief the latest developments in the understanding of mitochondrial pathogenesis in ALS and emphasize the restorative capacity of therapeutic candidates. Results: In ALS, mitochondrial dysfunction is a well-known phenomenon. Various therapies targeted towards mitochondrial dysfunction aim at decreasing ROS generation, increasing mitochondrial biogenesis, and inhibiting apoptotic pathways. Some of the therapies briefed in this review may be categorized as synthetic, natural compounds, genetic materials, and cellular therapies. Conclusion: The overarching goals of mitochondrial therapies in ALS are to benefit ALS patients by slowing down the disease progression and prolonging overall survival. Despite various therapeutic approaches, there are many hurdles in the development of a successful therapy due to the multifaceted nature of mitochondrial dysfunction and ALS progression. Intensive research is required to precisely elucidate the molecular pathways involved in the progression of mitochondrial dysfunctions that ultimately lead to ALS. Because of the multifactorial nature of ALS, a combination therapy approach may hold the key to cure and treat ALS in the future.
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spelling pubmed-102865902023-10-12 Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis Dhasmana, Swati Dhasmana, Anupam Kotnala, Sudhir Mangtani, Varsha Narula, Acharan S. Haque, Shafiul Jaggi, Meena Yallapu, Murali M. Chauhan, Subhash C. Curr Neuropharmacol Neurology Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive and terminal neurodegenerative disorder. Mitochondrial dysfunction, imbalance of cellular bioenergetics, electron chain transportation and calcium homeostasis are deeply associated with the progression of this disease. Impaired mitochondrial functions are crucial in rapid neurodegeneration. The mitochondria of ALS patients are associated with deregulated Ca(2+) homeostasis and elevated levels of reactive oxygen species (ROS), leading to oxidative stress. Overload of mitochondrial calcium and ROS production leads to glutamate-receptor mediated neurotoxicity. This implies mitochondria are an attractive therapeutic target. Objective: The aim of this review is to brief the latest developments in the understanding of mitochondrial pathogenesis in ALS and emphasize the restorative capacity of therapeutic candidates. Results: In ALS, mitochondrial dysfunction is a well-known phenomenon. Various therapies targeted towards mitochondrial dysfunction aim at decreasing ROS generation, increasing mitochondrial biogenesis, and inhibiting apoptotic pathways. Some of the therapies briefed in this review may be categorized as synthetic, natural compounds, genetic materials, and cellular therapies. Conclusion: The overarching goals of mitochondrial therapies in ALS are to benefit ALS patients by slowing down the disease progression and prolonging overall survival. Despite various therapeutic approaches, there are many hurdles in the development of a successful therapy due to the multifaceted nature of mitochondrial dysfunction and ALS progression. Intensive research is required to precisely elucidate the molecular pathways involved in the progression of mitochondrial dysfunctions that ultimately lead to ALS. Because of the multifactorial nature of ALS, a combination therapy approach may hold the key to cure and treat ALS in the future. Bentham Science Publishers 2023-04-12 2023-04-12 /pmc/articles/PMC10286590/ /pubmed/36111770 http://dx.doi.org/10.2174/1570159X20666220915092703 Text en © 2023 Bentham Science Publishers https://creativecommons.org/licenses/by/4.0/© 2023 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode)
spellingShingle Neurology
Dhasmana, Swati
Dhasmana, Anupam
Kotnala, Sudhir
Mangtani, Varsha
Narula, Acharan S.
Haque, Shafiul
Jaggi, Meena
Yallapu, Murali M.
Chauhan, Subhash C.
Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis
title Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis
title_full Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis
title_fullStr Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis
title_full_unstemmed Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis
title_short Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis
title_sort boosting mitochondrial potential: an imperative therapeutic intervention in amyotrophic lateral sclerosis
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286590/
https://www.ncbi.nlm.nih.gov/pubmed/36111770
http://dx.doi.org/10.2174/1570159X20666220915092703
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