Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, India.
Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Erandwane, Pune, 411038, Maharashtra, India.
Curr Top Med Chem. 2022;22(22):1880-1896. doi: 10.2174/1568026622666220624155357.
Alzheimer's disease (AD) is a severe progressive neurodegenerative condition that shows misfolding and aggregation of proteins contributing to a decline in cognitive function involving multiple behavioral, neuropsychological, and cognitive domains. Multiple epi (genetic) changes and environmental agents have been shown to play an active role in ER stress induction. Neurodegeneration due to endoplasmic reticulum (ER) stress is considered one of the major underlying causes of AD. ER stress may affect essential cellular functions related to biosynthesis, assembly, folding, and post-translational modification of proteins leading to neuronal inflammation to promote AD pathology. Treatment with phytochemicals has been shown to delay the onset and disease progression and improve the well-being of patients by targeting multiple signaling pathways in AD. Phytochemical's protective effect against neuronal damage in AD pathology may be associated with the reversal of ER stress and unfolding protein response by enhancing the antioxidant and anti-inflammatory properties of the neuronal cells. Hence, pharmacological interventions using phytochemicals can be a potential strategy to reverse ER stress and improve AD management. Towards this, the present review discusses the role of phytochemicals in preventing ER stress in the pathology of AD.
阿尔茨海默病(AD)是一种严重的进行性神经退行性疾病,其特征是蛋白质错误折叠和聚集,导致认知功能下降,涉及多个行为、神经心理学和认知领域。多项 epi(遗传)变化和环境因素已被证明在 ER 应激诱导中发挥积极作用。内质网(ER)应激引起的神经退行性变被认为是 AD 的主要潜在原因之一。ER 应激可能会影响与生物合成、组装、折叠和蛋白质翻译后修饰相关的基本细胞功能,导致神经元炎症,从而促进 AD 病理学。研究表明,植物化学物质通过靶向 AD 中的多个信号通路,可延迟发病和疾病进展,并改善患者的健康状况。植物化学物质对 AD 病理学中神经元损伤的保护作用可能与通过增强神经元细胞的抗氧化和抗炎特性来逆转 ER 应激和未折叠蛋白反应有关。因此,使用植物化学物质进行药理学干预可能是一种逆转 ER 应激和改善 AD 管理的潜在策略。为此,本综述讨论了植物化学物质在预防 AD 病理学中 ER 应激中的作用。