Bioenergetic failure and oxidative stress: mitochondrial contributions to Alzheimer's disease

The pathophysiology of Alzheimer's disease (AD), a progressive neurodegenerative illness marked by memory loss and cognitive decline, is greatly impacted by mitochondrial dysfunction. Recent research suggests that a number of interconnected processes, such as elevated oxidative stress, disturbed energy metabolism, compromised calcium homeostasis, and malformed mitochondrial dynamics, all lead to neuronal injury. The mitochondria in AD brains have structural defects and the function of important oxidative phosphorylation-related enzymes is lowered, which results in less ATP being produced. Further exacerbated by mitochondrial dysfunction is the build-up of amyloid-beta (Aβ) peptides and hyperphosphorylated tau proteins, which interact directly with mitochondrial membranes and proteins to cause mitochondrial fragmentation and hinder mitochondrial transport along neuronal axons. These occurrences cause an increase in reactive oxygen species (ROS) generation, which exacerbates oxidative damage and feeds a vicious cycle. In AD, mutations in mitochondrial DNA (mtDNA) and changes in mitochondrial biogenesis have also been documented, indicating a key involvement in the development of the illness. Preclinical models show promise for therapeutic approaches that attempt to maintain mitochondrial function, including antioxidants, drugs that target the mitochondria. It is crucial to comprehend the intricate relationship between mitochondrial dysfunction and other pathological aspects of AD to find new treatment targets and enhance patient outcomes. In addition to underlining its role in the development of AD, this review examines the complex interaction between mitochondrial dysfunction and AD pathogenesis, taking into account its potential as a biomarker and a target for intervention.