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

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.

Integrative big transcriptomics data analysis implicates crucial role of MUC13 in pancreatic cancer

“…Additionally, male patients have shown higher expression level of MUC13 as compared to female patients. The reason for this male vs female disparity could be due to protective female hormones [27] . According our analysis, alcohol consumption, diabetic status and inflammation in pancreas may also be responsible for the higher MUC13 expression in PanCa patients.…”

Trimetazidine Improves Mitochondrial Dysfunction in SOD1G93A Cellular Models of Amyotrophic Lateral Sclerosis through Autophagy Activation

“…In fact, the mitochondrial alterations linked to a failure in glucose metabolism could hinder the motor unit from meeting the actual energy needs, triggering a vicious cycle where the increased utilization of fatty acids as fuel attempts to compensate for the energy deficits [ 15 , 16 , 17 ]. In this context, boosting mitochondrial metabolism with targeted pharmacological approaches could improve energy failures that appear early in ALS [ 18 , 19 , 20 , 21 ]. Therefore, in this clinical framework, drugs that act as metabolic modulators capable of targeting mitochondria and improving energy metabolism could be beneficial for ALS therapy.…”

Mitochondrial Medicine for Neurological Disorders

“…In this article, Dhasmana et al , [ 3 ] summarized the recent advancements in mitochondrial pathophysiology and therapeutics potential of mitochondrial therapies in amyotrophic lateral sclerosis.…”