Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey.
Fundam Clin Pharmacol. 2023 Jun;37(3):397-427. doi: 10.1111/fcp.12861. Epub 2023 Jan 13.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment so widespread that it interferes with a person's ability to complete daily activities. AD is becoming increasingly common, and it is estimated that the number of patients will reach 152 million by 2050. Current treatment options for AD are symptomatic and have modest benefits. Therefore, considering the human, social, and economic burden of the disease, the development of drugs with the potential to alter disease progression has become a global priority. In this review, the molecular mechanisms involved in the pathology of AD were evaluated as therapeutic targets. The main aim of the review is to focus on new knowledge about mitochondrial dysfunction, oxidative stress, and neuronal transmission in AD, as well as a range of cellular signaling mechanisms and associated treatments. Important molecular interactions leading to AD were described in amyloid cascade and in tau protein function, oxidative stress, mitochondrial dysfunction, cholinergic and glutamatergic neurotransmission, cAMP-regulatory element-binding protein (CREB), the silent mating type information regulation 2 homolog 1 (SIRT-1), neuroinflammation (glial cells), and synaptic alterations. This review summarizes recent experimental and clinical research in AD pathology and analyzes the potential of therapeutic applications based on molecular disease mechanisms.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是认知障碍广泛，以至于干扰了患者完成日常活动的能力。AD 的发病率越来越高，据估计，到 2050 年，患者人数将达到 1.52 亿。目前 AD 的治疗选择是对症治疗，且效果有限。因此，考虑到疾病对人类、社会和经济的负担，开发具有改变疾病进程潜力的药物已成为全球的首要任务。在这篇综述中，评估了 AD 病理学中的分子机制作为治疗靶点。本篇综述的主要目的是关注 AD 中线粒体功能障碍、氧化应激和神经元传递方面的新知识，以及一系列细胞信号转导机制和相关治疗方法。描述了导致 AD 的重要分子相互作用，包括淀粉样蛋白级联和 tau 蛋白功能、氧化应激、线粒体功能障碍、胆碱能和谷氨酸能神经传递、环磷酸腺苷调节元件结合蛋白（CREB）、沉默交配型信息调节 2 同源物 1（SIRT-1）、神经炎症（神经胶质细胞）和突触改变。本文综述了 AD 病理学的最新实验和临床研究，并分析了基于分子疾病机制的治疗应用的潜力。
