Yadav Ekta, Mandal Ashok Kumar, Sah Ajay Kumar, Poudel Sandesh, Pathak Prateek, Khalilullah Habibullah, Jaremko Mariusz, Emwas Abdul-Hamid, Yadav Pankajkumar, Verma Amita
Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, 211007, India.
Natural Product Research Laboratory, Thapathali, Kathmandu 44600, Nepal.
CNS Neurol Disord Drug Targets. 2024 Sep 18. doi: 10.2174/0118715273298025240905130205.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes atrophy of brain cells, leading to their death, and has become a leading cause of death in aging populations worldwide. AD is characterized by β-amyloid (Aβ) deposition and tau phosphorylation in neural tissues, but the precise pathophysiology of the disease is still obscure. Autophagy is an evolutionarily targeted mechanism that is necessary for the elimination of neuronal and glial misfolded proteins as well as proteins. It also plays an essential role in synaptic plasticity. The aberrant autophagy primarily influences the process of aging and neurodegeneration. Autophagy significantly influences how Aβ and tau function physiologically, therefore, atypical autophagy is expected to perform an important role in Aβ deposition and tau phosphorylation characteristic in the development of AD. Bioactive phytoconstituents could majorly contribute as a natural yet effective alternative approach to slow down the progression of neurodegeneration and promote the active aging process in elderly patients. Over the recent years, it is well evidenced that different secondary metabolites including polyphenols, alkaloids, terpenes, and phenols exhibited neuroprotective effects, and attenuated brain damage, and cognitive impairment in vitro as well as in vivo. Additionally, the underlying mechanism of action shared by them is the regulation of competent autophagy via the removal of aggregated protein and mitochondrial dysfunction. The present article is structured as a reference for researchers keen to investigate and assess the new natural compound-mediated therapeutic approach for AD treatment through the modulation of autophagy.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，可导致脑细胞萎缩，进而死亡，已成为全球老年人群的主要死因。AD的特征是神经组织中β-淀粉样蛋白（Aβ）沉积和tau蛋白磷酸化，但其确切的病理生理学仍不清楚。自噬是一种进化上有针对性的机制，对于清除神经元和胶质细胞中错误折叠的蛋白质以及其他蛋白质是必需的。它在突触可塑性中也起着至关重要的作用。异常自噬主要影响衰老和神经退行性变的过程。自噬显著影响Aβ和tau蛋白的生理功能，因此，非典型自噬有望在AD发展过程中的Aβ沉积和tau蛋白磷酸化特征中发挥重要作用。生物活性植物成分可能是一种天然且有效的替代方法，主要有助于减缓神经退行性变的进程，并促进老年患者的积极衰老过程。近年来，有充分证据表明，包括多酚、生物碱、萜类和酚类在内的不同次生代谢产物在体外和体内均表现出神经保护作用，减轻了脑损伤和认知障碍。此外，它们共有的潜在作用机制是通过清除聚集蛋白和线粒体功能障碍来调节自噬。本文旨在为热衷于研究和评估通过调节自噬来治疗AD的新型天然化合物介导的治疗方法的研究人员提供参考。
