The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.
The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Amman, JO · Author affiliation
Department of Physical Therapy, Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.Location evidence
Najaf, IQ · Author affiliation
College of pharmacy, the Islamic University, Najaf, Iraq.Location evidence
Al Diwaniyah, IQ · Author affiliation
Department of medical analysis, medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq.Location evidence
Baghdad, IQ · Author affiliation
Department of Medicinal chemistry, Al-Turath University, Al Mansour, Baghdad, 10013, Iraq.Location evidence
IN · Author affiliation · country only
Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.Location evidence
Bhubaneswar, IN · Author affiliation
Department of General Medicine, IMS and SUM Hospital, Siksha 'O' Anusandhan, Bhubaneswar, Odisha, 751003, India.Location evidence
Chennai, IN · Author affiliation
Department of Nursing, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India.Location evidence
Chandigarh, IN · Author affiliation
Department of Physiotherapy, University Institute of Allied Health Sciences, Chandigarh University, Mohali, Punjab, India.Location evidence
Mohali, IN · Author affiliation
Department of Physiotherapy, University Institute of Allied Health Sciences, Chandigarh University, Mohali, Punjab, India.Location evidence
Dehradun, IN · Author affiliation
School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India. aashna07sinha@gmail.com.Location evidence
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Original abstract
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, remain leading causes of disability and premature death. Although they present with distinct clinical phenotypes, they converge on several pathogenic processes. Among these, mitochondrial dysfunction has emerged as a key driver of neurodegeneration, encompassing impaired bioenergetic capacity, disturbed calcium handling, altered mitochondrial dynamics, insufficient mitophagy, and excessive production of reactive oxygen species (ROS). This review provides a focused synthesis of the ways in which mitochondrial pathology contributes to neurodegeneration across major neurodegenerative disorders and summarizes therapeutic strategies designed to target mitochondria. We outline disease-relevant mitochondrial abnormalities and connect them to neuronal loss, synaptic failure, and neuroinflammatory cascades, with particular attention to mitochondrial ROS and inflammatory signaling linked to mitochondrial DNA. The manuscript further evaluates current and emerging interventions, including mitochondria-targeted antioxidants, mitochondrial transfer/transplantation, exercise, dietary approaches, and nanotechnology-enabled delivery systems. For each strategy, we consider the mechanistic rationale, key preclinical findings, and barriers to translation. Across experimental models, many of these approaches confer measurable neuroprotection-often reflected by lower oxidative burden, stabilization of mitochondrial membrane potential, and partial restoration of ATP production. However, clinical findings have been inconsistent, suggesting that efficacy depends strongly on disease stage, patient heterogeneity, and the specific mitochondrial defect being targeted. By integrating mechanistic insights with therapeutic evidence, this review offers a structured perspective on shared and disease-specific features of mitochondrial dysfunction and highlights priorities for advancing mitochondria-centered interventions toward meaningful clinical benefit.