Title:Mitochondrial Dysfunction in Alzheimer’s Disease: Opportunities for
Drug Development
Volume: 20
Issue: 4
Author(s): Shiveena Bhatia, Rishi Rawal, Pratibha Sharma, Tanveer Singh, Manjinder Singh*Varinder Singh*
Affiliation:
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
Keywords:
Alzheimer’s disease, apoptosis, β-amyloid plaques, mitochondrial dysfunction, oxidative stress, tau proteins.
Abstract: Alzheimer’s disease (AD) is one of the major reasons for 60-80% cases of senile dementia
occurring as a result of the accumulation of plaques and tangles in the hippocampal and cortical
neurons of the brain leading to neurodegeneration and cell death. The other pathological features of
AD comprise abnormal microvasculature, network abnormalities, interneuronal dysfunction, increased
β-amyloid production and reduced clearance, increased inflammatory response, elevated production of
reactive oxygen species, impaired brain metabolism, hyperphosphorylation of tau, and disruption of
acetylcholine signaling. Among all these pathologies, Mitochondrial Dysfunction (MD), regardless of it
being an inciting insult or a consequence of the alterations, is related to all the associated AD pathologies.
Observed altered mitochondrial morphology, distribution and movement, increased oxidative stress,
dysregulation of enzymes involved in mitochondrial functioning, impaired brain metabolism, and
impaired mitochondrial biogenesis in AD subjects suggest the involvement of mitochondrial malfunction
in the progression of AD. Here, various pre-clinical and clinical evidence establishing MD as a key
mediator in the progression of neurodegeneration in AD are reviewed and discussed with an aim to foster
future MD based drug development research for the management of AD.
