Mitochondria in crisis: The hidden engine of neurodegenration

The pathogenesis of major neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and other age-related cognitive decline syndromes, is now known to be greatly impacted by mitochondrial malfunction. This study thoroughly investigates the complex function of mitochondria as signaling hubs and energy regulators in brain health, as well as how their dysregulation may either be the fundamental cause or a contributing factor to neurodegenerative cascades. Following the evaluation of mitochondrial bioenergetics and redox balance, the discussion shifts to the emerging field of mitochondrial epigenetics, which focuses on alterations in non-coding RNAs, mtDNA methylation, and histone modifications that impact the risk of neurodegenerative disorders.. The interplay of mitochondrial calcium homeostasis, oxidative stress, and apoptotic signals is examined, in addition to the several roles of sirtuins, particularly SIRT1 and SIRT2, in controlling neuronal fate under oxidative stress. The idea of mitochondrial entropy in aging brains is further explored in this review, which connects energy failure to the breakdown of proteostasis and cognitive decline. It emphasizes how crucial mitochondrial dysfunction is at the "crossroads" of oxidative stress and neurodegeneration, proving that it is frequently the underlying cause rather than just a symptom. Targeted mitochondrial therapies are suggested as a potential avenue for precision neuroprotection in the future, with particular focus paid to hemisphere-specific vulnerabilities in brain diseases. Through the integration of molecular insights with new therapeutic approaches, such as mitochondrial antioxidants, mitophagy enhancement, and nanocarrier-mediated delivery, this work promotes mitochondria-focused intervention as a game-changing method for slowing or stopping the progression of neurodegenerative diseases.