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

Swati      Dhasmana; Anupam      Dhasmana; Sudhir      Kotnala; Varsha      Mangtani; Acharan   S.   Narula; Shafiul      Haque; Meena      Jaggi; Murali   M.   Yallapu; Subhash   C.   Chauhan
Abstract

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 Ca²⁺ homeostasis and elevated levels of reactive oxygen species (ROS), leading to oxidative stress. Overload of mitochondrial calcium and ROS production leads to glutamatereceptor 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.
Keywords: ALS, mitochondrial dysfunction, neurodegeneration, ROS in ALS, excitotoxicity, mitochondrial biogenesis, mitochondrial reactivation.
Graphical Abstract

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Cite As
Current Neuropharmacology

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

Abstract

Graphical Abstract
