Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential

Zhang, Wei1,2; Xu, Chengchao1,3; Sun, Jichao1; Shen, Han-Ming4; Wang, Jigang1,3,5; Yang, Chuanbin1

2022-03-01

10.1016/j.apsb.2022.01.008

Acta Pharmaceutica Sinica B   影响因子和分区

2211-3835

2211-3843

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (A beta) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy - lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy - lysosomal pathway in AD. We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins, A beta and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy -lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Alzheimer's disease (AD) Amyloid beta (A beta) peptides MAPT/tau Autophagy-lysosomal pathway Autophagy enhancers Autophagy Mitophagy Neurodegenerative diseases

SCI

英语

ESI高被引

第一 ; 通讯

National Natural Science Foundation of China[82003721,82071193,32170774,32000673] ; Shenzhen Science and Technology Innovation Commission (China)[JCYJ20210324114014039] ; China Postdoctoral Science Foundation[2020M683182] ; Guangdong Basic and Applied Basic Research Foundation (China)[2020A1515110549]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000779794500002

INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Clin Med Coll 2,Affiliated Hosp 1, Dept Geriatr,Shenzhen Peoples Hosp, Shenzhen 518020, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
3.China Acad Chinese Med Sci, Artemisinin Res Ctr, Inst Chinese Mat Med, Beijing 100700, Peoples R China
4.Univ Macau, Fac Hlth Sci, Taipa 999078, Macao, Peoples R China
5.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China

Zhang, Wei,Xu, Chengchao,Sun, Jichao,et al. Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential[J]. Acta Pharmaceutica Sinica B,2022,12(3).

Zhang, Wei,Xu, Chengchao,Sun, Jichao,Shen, Han-Ming,Wang, Jigang,&Yang, Chuanbin.(2022).Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential.Acta Pharmaceutica Sinica B,12(3).

Zhang, Wei,et al."Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential".Acta Pharmaceutica Sinica B 12.3(2022).