坏死性凋亡在阿尔茨海默病中的分子机制与治疗策略  

Molecular mechanism and therapeutic strategies of necrotic apoptosis in Alzheimer’s disease

作　　者：陆志成 唐丽娜 莫圣龙 杨成敏 简崇东[2] 商敬伟 LU Zhi-cheng;TANG Li-na;MO Sheng-long;YANG Cheng-min;JIAN Chong-dong;SHANG Jing-wei(Graduate School of Youjiang Medical University for Nationalities,Guangxi Baise 533000,China;Department of Neurology,Affiliated Hospital of Youjiang Medical University for Nationalities,Guangxi Baise 533000,China)

机构地区：[1]右江民族医学院研究生学院,广西百色533000 [2]右江民族医学院附属医院神经内科,广西百色533000

出　　处：《解剖学报》2025年第2期239-247,共9页Acta Anatomica Sinica

基　　金：国家自然科学基金(82160254);右江民族医学院附属医院高层次人才科研项目(R20213001);百色市科学研究与技术开发计划课题(百科20224117)。

摘　　要：本综述深入探讨了坏死性凋亡在阿尔茨海默病(AD)中的关键作用,并以治疗策略、药物研发、前景与挑战等方面为基点,突出其在疾病发展中的重要性。首先,坏死性凋亡在AD的发病机制中扮演重要角色,特别是与β-淀粉样蛋白(Aβ)和Tau蛋白的异常代谢紧密相连。药物设计的主要焦点是调节这两种蛋白的代谢途径,以期减缓或抑制坏死性凋亡的进展。其次,药物研发方面取得的进展进一步凸显了坏死性凋亡在治疗AD中的重要性。当前的研究主要集中在影响Aβ和Tau蛋白代谢的药物上,例如仑卡奈单抗(lecanemab),但面临着一些不一致的结果,强调对坏死性凋亡分子机制更全面的了解是必要的。最后,对AD中坏死性凋亡研究的前景与挑战进行了深入探讨。深入理解坏死性凋亡不仅有助于深化对AD病理机制的认识,也可能揭示新的治疗靶点。然而,面临多因素影响和治疗时机选择的挑战,需要未来更为深入的研究。综合而言,本综述呼吁,未来研究应更深入地理解坏死性凋亡的分子机制,加强治疗策略研究,深入了解其与其他细胞死亡途径的交叉调控,同时促进基础研究与临床实践之间的合作,推动对阿尔茨海默病和坏死性凋亡的全面理解和治疗手段的不断拓展。This review delves into the pivotal role of necrotic apoptosis in Alzheimer’s disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism ofβ⁃amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβand Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in⁃depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross⁃regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer’s disease and necrotic apoptosis.

关 键 词：阿尔茨海默病 坏死性凋亡 Β-淀粉样蛋白 TAU蛋白 

分 类 号：R741[医药卫生—神经病学与精神病学]