Chitkara College of Pharmacy, Chitkara University, Punjab, India.
School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.
Curr Neuropharmacol. 2022;20(4):675-692. doi: 10.2174/1570159X19666210517114016.
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.
阿尔茨海默病（AD）是导致 60-80%老年痴呆症的主要原因之一，其发生是由于大脑海马体和皮质神经元中斑块和缠结的积累导致神经退行性变和细胞死亡。AD 的其他病理特征包括异常微血管、网络异常、中间神经元功能障碍、β-淀粉样蛋白产生增加和清除减少、炎症反应增加、活性氧产生增加、脑代谢受损、tau 过度磷酸化以及乙酰胆碱信号转导中断。在所有这些病理变化中，线粒体功能障碍（MD）无论它是一个激发性损伤还是改变的结果，都与所有相关的 AD 病理变化有关。在 AD 患者中观察到的线粒体形态、分布和运动改变、氧化应激增加、参与线粒体功能的酶失调、脑代谢受损以及线粒体生物发生受损提示线粒体功能障碍参与了 AD 的进展。在这里，我们回顾并讨论了各种临床前和临床证据，这些证据将 MD 确立为 AD 神经退行性变进展的关键介质，旨在促进未来基于 MD 的药物开发研究，以管理 AD。
