Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

被引：651

作者：

Galluzzi, Lorenzo ^{[1
,2
]}

Bravo-San Pedro, Jose Manuel ^{[2
,3
,4
,5
,6
,7
]}

Levine, Beth ^{[8
,9
]}

Green, Douglas R. ^{[10
]}

Kroemer, Guido ^{[2
,3
,4
,5
,6
,7
,11
,12
]}

机构：

[1] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY 10065 USA

[2] Univ Paris Descartes Paris V, Sorbonne Paris Cite, F-75006 Paris, France

[3] Univ Pierre & Marie Curie Paris VI, F-75006 Paris, France

[4] Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, F-75006 Paris, France

[5] INSERM, U1138, F-75006 Paris, France

[6] Gustave Roussy Comprehens Canc Inst, Metabol Platform, F-94805 Villejuif, France

[7] Gustave Roussy Comprehens Canc Inst, Cell Biol Platform, F-94805 Villejuif, France

[8] Univ Texas Southwestern Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA

[9] Howard Hughes Med Inst, Dallas, TX 75390 USA

[10] St Jude Childrens Res Hosp, Memphis, TN 38105 USA

[11] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, S-17176 Stockholm, Sweden

[12] Hop Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France

来源：

NATURE REVIEWS DRUG DISCOVERY | 2017年 / 16卷 / 07期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; ACTIVATED PROTEIN-KINASE; FOCAL CEREBRAL-ISCHEMIA; LIFE-SPAN EXTENSION; TRAUMATIC BRAIN-INJURY; INDUCED PULMONARY-HYPERTENSION; BECLIN 1-DEPENDENT AUTOPHAGY; ATTENUATES RENAL HYPERTROPHY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MPTP-INDUCED PARKINSONISM;

D O I：

10.1038/nrd.2017.22

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic.

引用

页码：487 / 511

页数：25

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