School of Pharmacy and Technology Management, SVKMs NMIMS University, Shirpur campus, Maharastra India.
Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan.
Brain Res. 2024 Dec 1;1844:149165. doi: 10.1016/j.brainres.2024.149165. Epub 2024 Aug 20.
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by abnormal accumulation of tau proteins and amyloid-β, leading to neuronal death and cognitive impairment. Recent studies have implicated aging pathways, including dysregulation of tau and cellular senescence in AD pathogenesis. In AD brains, tau protein, which normally stabilizes microtubules, becomes hyperphosphorylated and forms insoluble neurofibrillary tangles. These tau aggregates impair neuronal function and are propagated across the brain's neurocircuitry. Meanwhile, the number of senescent cells accumulating in the aging brain is rising, releasing a pro-inflammatory SASP responsible for neuroinflammation and neurodegeneration. This review explores potential therapeutic interventions for AD targeting tau protein and senescent cells, and tau -directed compounds, senolytics, eliminating senescent cells, and agents that modulate the SASP-senomodulators. Ultimately, a combined approach that incorporates tau-directed medications and targeted senescent cell-based therapies holds promise for reducing the harmful impact of AD's shared aging pathways.
阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，其特征是 Tau 蛋白和淀粉样蛋白-β的异常积累，导致神经元死亡和认知障碍。最近的研究表明，衰老途径，包括 Tau 蛋白的失调和细胞衰老，与 AD 的发病机制有关。在 AD 大脑中，正常稳定微管的 Tau 蛋白过度磷酸化并形成不溶性神经原纤维缠结。这些 Tau 聚集物损害神经元功能，并在大脑的神经回路中传播。与此同时，衰老大脑中积累的衰老细胞数量正在增加，释放出一种促炎的 SASP，负责神经炎症和神经退行性变。这篇综述探讨了针对 Tau 蛋白和衰老细胞的 AD 潜在治疗干预措施，以及 Tau 定向化合物、衰老细胞清除剂和调节 SASP 的试剂——Senomodulators。最终，一种结合了 Tau 定向药物和针对衰老细胞的治疗方法的联合方法有望减轻 AD 共同的衰老途径的有害影响。
