Exploring Mitochondria in Neurodegenerative Disorders: Unveiling Mechanisms and Therapeutic Strategies

Dear Colleagues,

Mitochondria are vital organelles responsible for cellular energy production and the maintenance of cellular homeostasis. These dynamic structures play essential roles in various cellular processes, including ATP generation through oxidative phosphorylation, regulation of the cellular metabolic environment, and initiation of apoptosis. Dysfunction in mitochondrial operations has been increasingly recognized as a key factor in the development and progression of numerous neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

Mitochondrial Dynamics and Neurodegeneration

The health and function of neurons are intricately linked to the proper functioning of mitochondria. Mitochondrial dynamics, including fission, fusion, and transport within neurons, are crucial for meeting the high energy demands of these cells and for maintaining their physiological functions. Aberrations in these processes can lead to mitochondrial fragmentation, impaired bioenergetics, and the accumulation of damaged mitochondria, which in turn contribute to neuronal dysfunction and death. This Special Issue seeks to delve into these dynamic processes and their disruption in neurodegenerative diseases, providing a comprehensive overview of how mitochondrial dysfunction propagates neuronal degeneration.

Mitochondrial Dysfunction in Neurodegenerative Diseases

Alzheimer's Disease: In Alzheimer’s disease, mitochondrial dysfunction is evidenced by reduced oxidative phosphorylation, increased production of reactive oxygen species (ROS), and impaired mitochondrial dynamics. These alterations contribute to synaptic failure and neuronal death, hallmark features of the disease.

Parkinson's Disease: Mitochondrial defects, such as mutations in the genes encoding for mitochondrial proteins like Parkin and PINK1, lead to impaired mitochondrial quality control and increased vulnerability to oxidative stress, central features in the pathogenesis of Parkinson’s disease.

Amyotrophic Lateral Sclerosis (ALS): In ALS, mitochondrial dysfunction is linked to the accumulation of misfolded proteins, defective axonal transport of mitochondria, and impaired energy metabolism, all of which exacerbate motor neuron degeneration.

Impact on Neuronal Health

The maintenance of mitochondrial health is crucial for the survival and function of neurons. Disruptions in mitochondrial dynamics and function can lead to energy deficits, increased oxidative stress, and activation of cell death pathways. Understanding the molecular mechanisms underlying these processes is essential for developing targeted therapeutic interventions.

Potential Therapeutic Strategies

Given the central role of mitochondria in neurodegeneration, targeting mitochondrial dysfunction represents a promising therapeutic approach. Potential strategies include:

Enhancing Mitochondrial Biogenesis: Promoting the production of new mitochondria through the activation of pathways such as PGC-1α could help restore mitochondrial function and improve neuronal health.

Mitophagy Induction: Enhancing the selective degradation of damaged mitochondria through mitophagy can prevent the accumulation of dysfunctional mitochondria and reduce oxidative stress.

Antioxidant Therapies: Reducing oxidative stress by using antioxidants that specifically target mitochondria could protect neurons from oxidative damage.

Gene Therapy: Correcting mutations in mitochondrial genes or modulating the expression of mitochondrial proteins through gene therapy offers a potential avenue for treating mitochondrial dysfunction at its source.

Small Molecule Modulators: Developing small molecules that can modulate mitochondrial dynamics, improve bioenergetics, or enhance mitochondrial quality control mechanisms represents a promising area of therapeutic development.

Call for Contributions

This Special Issue invites researchers and clinicians to contribute original research articles, comprehensive reviews, and insightful perspectives that advance our understanding of the role of mitochondria in neurodegenerative disorders. We seek to compile a diverse collection of studies that offer novel insights into the mechanisms of mitochondrial dysfunction, explore its impact on neuronal health, and propose innovative therapeutic strategies targeting mitochondria.

Conclusion

Join us in this exciting Special Issue to further our knowledge of the intricate relationship between mitochondria and neurodegenerative diseases. By exploring the fundamental mechanisms and potential therapeutic interventions, we aim to pave the way for innovative treatments that could significantly improve the lives of individuals affected by these debilitating disorders. Your contributions will play a crucial role in advancing the field and fostering new avenues for research and therapy in neurodegeneration.

Dr. Saeid Ghavami
Dr. Mohamad-Reza Aghanoori
Guest Editors

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• neurodegenerative disorders
• energy homeostasis and metabolism
• mitochondrial dysfunction
• mitochondrial dynamics
• mitophagy and autophagy
• synaptic function
• axonal transport
• oxidative stress
• calcium homeostasis
• treatments targeting mitochondria
• mitochondrial biogenesis
• neuroprotection
• therapeutic strategies