Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules

Abstract

Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.

Allosteric Activation of SIRT1 by 2,4-Dihydroxy-azaflavanone Averts MPP+-Mediated Dysfunction in Mitochondrial Biogenesis and Bioenergetics: Implications for Parkinson’s Disease

“…Emerging reports indicate that there is an increased interest in exploring mitochondrial therapeutics for PD. ,,,− In this regard, mitochondria-targeted small molecules/antioxidants, mitochondrial uncouplers, agents that enhance the levels of PGC-1α and SIRT1, and synthetic STACs are being widely explored. − ,, Our present observations on the allosteric activation of SIRT1 by azaflavanone and its superior effects as compared to resveratrol could assist in designing novel STACs and also provide novel therapeutic options for PD and related mitochondrial disorders. ,,, …”

“…In order to mitigate the mitochondrial dysfunction in PD, various strategies have been employed over the years. Mitochondria-targeted antioxidants such as Mito-Q, mito-apocynin, mitoVitE, mitoTEMPOL, and mito-metformin were found to exhibit promising effects in mouse models of PD. ,, Similarly, uncouplers of mitochondrial respiration, such as embelin, mito-DNP, nitazoxanide, niclosamide etc., were found to be effective in nullifying mitochondrial ROS and related downstream abnormalities. ,, Also, some of the above compounds were found to confer neuroprotection in multiple neurodegenerative disorders . In recent years, there has been a growing interest in exploring the therapeutic potential of uncoupling proteins (UCPs) for the treatment of neurodegenerative diseases. , Given UCPs’ involvement in mitochondrial function and energy metabolism, UCP-based interventions have the potential to mitigate the neuronal dysfunction …”