Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics

被引：265

作者：

Ajoolabady, Amir ^{[1
]}

Wang, Shuyi ^{[1
,2
]}

Kroemer, Guido ^{[3
,4
,5
,6
,7
]}

Penninger, Josef M. ^{[8
,9
]}

Uversky, Vladimir N. ^{[10
,11
]}

Pratico, Domenico ^{[12
]}

Henninger, Nils ^{[13
,14
]}

Reiter, Russel J. ^{[15
]}

Bruno, Askiel ^{[16
]}

Joshipura, Kaumudi ^{[17
,18
]}

Aslkhodapasandhokmabad, Hamid ^{[19
]}

Klionsky, Daniel J. ^{[20
,21
,22
]}

Ren, Jun ^{[23
,24
]}

机构：

[1] Univ Wyoming, Coll Hlth Sci, Laramie, WY 82071 USA

[2] Shanghai Univ, Sch Med, Shanghai 200444, Peoples R China

[3] Univ Paris, Ctr Rech Conieliers, Equipe Labellisee Ligue Canc, Inst Univ France,Sorbonne Univ,INSERM,U 1138, Paris, France

[4] Inst Gustave Roussy, Metabol & Cell Biol Platforms, Villejuif, France

[5] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France

[6] Chinese Acad Med Sci, Suzhou Inst Syst Med, Suzhou, Peoples R China

[7] Karolinska Inst, Dept Womens & Childrens Hlth, Karolinska Univ Hosp, Stockholm, Sweden

[8] Vienna Bioctr VBC, Inst Mol Biotechnol, Austrian Acad Sci MBA, Vienna, Austria

[9] Univ British Columbia, Life Sci Inst, Dept Med Genet, Vancouver, BC, Canada

[10] Univ S Florida, Morsani Coll Med, Dept Mol Med, Tampa, FL USA

[11] Russian Acad Sci, Inst Biol Instrumentat, Fed Res Ctr, Pushchino Sci Ctr Biol Res, Pushchino 142290, Moscow Region, Russia

[12] Temple Univ, Alzheimers Ctr Temple, Lewis Katz Sch Med, Philadelphia, PA 19140 USA

[13] Univ Massachusetts, Dept Neurol, Worcester, MA USA

[14] Univ Massachusetts, Dept Psychiat, Worcester, MA USA

[15] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX USA

[16] Augusta Univ, Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA

[17] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[18] Univ Puerto Rico, Ctr Clin Res & Hlth Promot, Med Sci Campus, San Juan, PR 00936 USA

[19] Univ Visayas, Gullas Coll Med, Dionisio Jakosalern St, Cebu 6000, Cebu, Philippines

[20] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA

[21] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA

[22] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

[23] Univ Washington, Dept Lab Med & Pathol, Seattle, WA 98195 USA

[24] Fudan Univ, Shanghai Inst Cardiovasc Dis, Dept Cardiol, Zhongshan Hosp, Shanghai 200032, Peoples R China

来源：

PHARMACOLOGY & THERAPEUTICS | 2021年 / 225卷

基金：

国家重点研发计划; 奥地利科学基金会;

关键词：

Adaptive autophagy; Cell death; Cerebral I; R injury; Ischemic stroke; Maladaptive autophagy; ENDOTHELIAL GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; ENDOPLASMIC-RETICULUM STRESS; KINASE-DEPENDENT AUTOPHAGY; PROTECTS RAT-BRAIN; CELL-DEATH; ISCHEMIA/REPERFUSION INJURY; NEURONAL AUTOPHAGY; CONFERS NEUROPROTECTION; ATHEROSCLEROSIS RISK;

D O I：

10.1016/j.pharmthera.2021.107848

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as an essential cellular process to maintain cellular homeostasis and organismal survival. However, unchecked or excessive induction of autophagy has been perceived to be detrimental and its contribution to neuronal cell death remains largely unknown. In this review, we will summarize the role of autophagy in IS, and discuss potential strategies, particularly, employment of natural compounds for IS treatment through manipulation of autophagy. (c) 2021 Elsevier Inc. All rights reserved.

引用

页数：23

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