Title:Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention
in Amyotrophic Lateral Sclerosis
Volume: 21
Issue: 5
Author(s): Swati Dhasmana, Anupam Dhasmana, Sudhir Kotnala, Varsha Mangtani, Acharan S. Narula, Shafiul Haque, Meena Jaggi, Murali M. Yallapu and Subhash C. Chauhan*
Affiliation:
- Department of Immunology & Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen,
Texas, TX, USA
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio
Grande Valley, McAllen, TX 78504, USA
Keywords:
ALS, mitochondrial dysfunction, neurodegeneration, ROS in ALS, excitotoxicity, mitochondrial biogenesis, mitochondrial reactivation.
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.