Mitochondria Modulating Therapeutic Approaches in the Management of Huntington’s Disease

Mitochondrial dysfunctions are considered epistatic to cellular malfunctions during advancement of neurodegenerative disorders, including Huntington's disease (HD). In HD, such compromised mitochondrial functioning contributes to perturb neuronal functioning via unwarranted free radicals generation, reduced ATP production, altered mitochondrial permeability transition and enhanced mitochondrial DNA lesions with concomitant failure in mitochondrial dynamics. Available pharmacological interventions in controlling HD progression are focused mainly in managing symptoms observed in HD, with limited ability to ameliorate behavioral and cognitive dysfunctions. Mitochondria targeted pharmacological molecules are now being considered as potent therapeutic interventions to efficiently ameliorate mitochondrial dysfunctions observed in HD, though this approach is still at its inception. Therefore, it is necessary to screen potent drug molecule/s which could be supplemented alone or in combination, and assist in managing HD. This review highlights the therapeutic potential of mitochondrial drug targeting and limitations of currently available mitochondria-targeted drugs (synthetic and natural antioxidants) under investigation in treating HD, encouraging the demand for designing perspective therapeutic strategies targeting mitochondria in efficient management of HD.