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近年来对阿尔茨海默病的认识进展:危险因素、亚型、药物靶点和潜在治疗方法。

Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics.

机构信息

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

Department of Basic Medical Science, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.

出版信息

Ageing Res Rev. 2024 Nov;101:102476. doi: 10.1016/j.arr.2024.102476. Epub 2024 Aug 31.

Abstract

Alzheimer's disease (AD) is a significant neocortical degenerative disorder characterized by the progressive loss of neurons and secondary alterations in white matter tracts. Understanding the risk factors and mechanisms underlying AD is crucial for developing effective treatments. The risk factors associated with AD encompass a wide range of variables, including gender differences, family history, and genetic predispositions. Additionally, environmental factors such as air pollution and lifestyle-related conditions like cardiovascular disease, gut pathogens, and liver pathology contribute substantially to the development and progression of AD and its subtypes. This review provides current update and deeper insights into the role of diverse risk factors, categorizing AD into its distinct subtypes and elucidating their specific pathophysiological mechanisms. Unlike previous studies that often focus on isolated aspects of AD, our review integrates these factors to offer a comprehensive understanding of the disease. Furthermore, the review explores a variety of drug targets linked to the neuropathology of different AD subtypes, highlighting the potential for targeted therapeutic interventions. We further discussed the novel therapeutic options and categorized them according to their targets. The roles of different drug targets were comprehensively studied, and the mechanism of action of their inhibitors was discussed in detail. By comprehensively covering the interplay of risk factors, subtype differentiation, and drug targets, this review provides a deeper understanding of AD and suggests directions for future research and therapeutic strategies.

摘要

阿尔茨海默病(AD)是一种重要的皮质下退行性疾病,其特征为神经元进行性丧失和白质束的继发性改变。了解 AD 的风险因素和发病机制对于开发有效的治疗方法至关重要。与 AD 相关的风险因素包括广泛的变量,包括性别差异、家族史和遗传易感性。此外,环境因素如空气污染和与生活方式相关的条件,如心血管疾病、肠道病原体和肝脏病理学,对 AD 及其亚型的发生和发展有很大影响。本综述提供了 AD 相关风险因素的最新进展和更深入的见解,将 AD 分为不同的亚型,并阐明其特定的病理生理机制。与以往经常关注 AD 孤立方面的研究不同,我们的综述整合了这些因素,以全面了解该疾病。此外,该综述探讨了与不同 AD 亚型神经病理学相关的多种药物靶点,强调了针对这些靶点进行治疗干预的潜力。我们还进一步讨论了新型治疗选择,并根据其靶点对其进行了分类。综合研究了不同药物靶点的作用,详细讨论了其抑制剂的作用机制。通过全面涵盖风险因素、亚型分化和药物靶点的相互作用,本综述深入了解了 AD,并提出了未来研究和治疗策略的方向。

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