Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai, China.
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Cell Death Dis. 2022 Aug 15;13(8):706. doi: 10.1038/s41419-022-05153-5.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of Aβ to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the unique role of ER stress in AD pathogenesis, reviewing key findings, and existing controversy in an attempt to summarize plausible therapeutic interventions in the management of AD pathophysiology.
阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，其特征是记忆和认知功能逐渐丧失，这给全球的医疗保健系统带来了沉重的负担。目前仍在开发用于干预 AD 潜在疾病进程的治疗方法。尽管许多努力都集中在 Aβ 的毒性形式上，以有效治疗 AD，但考虑到迄今为止的结果并不令人满意，检查其他靶点和治疗方法也很重要。内质网（ER）应激是指 ER 内未折叠或错误折叠的蛋白质堆积，从而扰乱 ER 和细胞内稳态。新出现的证据表明 ER 应激有助于 AD 的发病和发展。深入阐明 AD 病理学中的 ER 应激机制可能有助于为这种破坏性疾病的管理开辟新的治疗途径，以缓解认知痴呆症状。本文旨在解析 ER 应激在 AD 发病机制中的独特作用，综述关键发现和现有争议，试图总结 AD 病理生理学管理中合理的治疗干预措施。
