Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

被引：811

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：

美国国家卫生研究院; 欧洲研究理事会;

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 [微生物学]; 090105 [作物生产系统与生态工程];

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

共 300 条

[51]

Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates [J].

Egan, Daniel F. ;

Chun, Matthew G. H. ;

Vamos, Mitchell ;

Zou, Haixia ;

Rong, Juan ;

Miller, Chad J. ;

Lou, Hua Jane ;

Raveendra-Panickar, Dhanya ;

Yang, Chih-Cheng ;

Sheffler, Douglas J. ;

Teriete, Peter ;

Asara, John M. ;

Turk, Benjamin E. ;

Cosford, Nicholas D. P. ;

Shaw, Reuben J. .

MOLECULAR CELL, 2015, 59 (02) :285-297

[52]

Cardioprotection and lifespan extension by the natural polyamine spermidine [J].

Eisenberg, Tobias ;

Abdellatif, Mahmoud ;

Schroeder, Sabrina ;

Primessnig, Uwe ;

Stekovic, Slaven ;

Pendl, Tobias ;

Harger, Alexandra ;

Schipke, Julia ;

Zimmermann, Andreas ;

Schmidt, Albrecht ;

Tong, Mingming ;

Ruckenstuhl, Christoph ;

Dammbrueck, Christopher ;

Gross, Angelina S. ;

Herbst, Viktoria ;

Magnes, Christoph ;

Trausinger, Gert ;

Narath, Sophie ;

Meinitzer, Andreas ;

Hu, Zehan ;

Kirsch, Alexander ;

Eller, Kathrin ;

Carmona-Gutierrez, Didac ;

Buettner, Sabrina ;

Pietrocola, Federico ;

Knittelfelder, Oskar ;

Schrepfer, Emilie ;

Rockenfeller, Patrick ;

Simonini, Corinna ;

Rahn, Alexandros ;

Horsch, Marion ;

Moreth, Kristin ;

Beckers, Johannes ;

Fuchs, Helmut ;

Gailus-Durner, Valerie ;

Neff, Frauke ;

Janik, Dirk ;

Rathkolb, Birgit ;

Rozman, Jan ;

de Angelis, Martin Hrabe ;

Moustafa, Tarek ;

Haemmerle, Guenter ;

Mayr, Manuel ;

Willeit, Peter ;

von Frieling-Salewsky, Marion ;

Pieske, Burkert ;

Scorrano, Luca ;

Pieber, Thomas ;

Pechlaner, Raimund ;

Willeit, Johann .

NATURE MEDICINE, 2016, 22 (12) :1428-+

[53]

Induction of autophagy by spermidine promotes longevity [J].

Eisenberg, Tobias ;

Knauer, Heide ;

Schauer, Alexandra ;

Buettner, Sabrina ;

Ruckenstuhl, Christoph ;

Carmona-Gutierrez, Didac ;

Ring, Julia ;

Schroeder, Sabrina ;

Magnes, Christoph ;

Antonacci, Lucia ;

Fussi, Heike ;

Deszcz, Luiza ;

Hartl, Regina ;

Schraml, Elisabeth ;

Criollo, Alfredo ;

Megalou, Evgenia ;

Weiskopf, Daniela ;

Laun, Peter ;

Heeren, Gino ;

Breitenbach, Michael ;

Grubeck-Loebenstein, Beatrix ;

Herker, Eva ;

Fahrenkrog, Birthe ;

Froehlich, Kai-Uwe ;

Sinner, Frank ;

Tavernarakis, Nektarios ;

Minois, Nadege ;

Kroemer, Guido ;

Madeo, Frank .

NATURE CELL BIOLOGY, 2009, 11 (11) :1305-U102

[54]

Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia [J].

Ejlerskov, Patrick ;

Hultberg, Jeanette Goransdotter ;

Wang, JunYang ;

Carlsson, Robert ;

Ambjorn, Malene ;

Kuss, Martin ;

Liu, Yawei ;

Porcu, Giovanna ;

Kolkova, Kateryna ;

Rundsten, Carsten Friis ;

Ruscher, Karsten ;

Pakkenberg, Bente ;

Goldmann, Tobias ;

Loreth, Desiree ;

Prinz, Marco ;

Rubinsztein, David C. ;

Issazadeh-Navikas, Shohreh .

CELL, 2015, 163 (02) :324-339

[55]

Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy [J].

Eng, Christina H. ;

Wang, Zuncai ;

Tkach, Diane ;

Toral-Barza, Lourdes ;

Ugwonali, Savuth ;

Liu, Shanming ;

Fitzgerald, Stephanie L. ;

George, Elizabeth ;

Frias, Elizabeth ;

Cochran, Nadire ;

De Jesus, Rowena ;

McAllister, Gregory ;

Hoffman, Gregory R. ;

Bray, Kevin ;

Lemon, LuAnna ;

Lucas, Judy ;

Fantin, Valeria R. ;

Abraham, Robert T. ;

Murphy, Leon O. ;

Nyfeler, Beat .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (01) :182-187

[56]

Rapamycin is a neuroprotective treatment for traumatic brain injury [J].

Erlich, S. ;

Alexandrovich, A. ;

Shohami, E. ;

Pinkas-Kramarski, R. .

NEUROBIOLOGY OF DISEASE, 2007, 26 (01) :86-93

[57]

Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation [J].

Esposito, Marianna ;

Ruffini, Francesca ;

Bellone, Matteo ;

Gagliani, Nicola ;

Battaglia, Manuela ;

Martino, Gianvito ;

Furlan, Roberto .

JOURNAL OF NEUROIMMUNOLOGY, 2010, 220 (1-2) :52-63

[58]

SQSTM1 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis [J].

Fecto, Faisal ;

Yan, Jianhua ;

Vemula, S. Pavan ;

Liu, Erdong ;

Yang, Yi ;

Chen, Wenjie ;

Zheng, Jian Guo ;

Shi, Yong ;

Siddique, Nailah ;

Arrat, Hasan ;

Donkervoort, Sandra ;

Ajroud-Driss, Senda ;

Sufit, Robert L. ;

Heller, Scott L. ;

Deng, Han-Xiang ;

Siddique, Teepu .

ARCHIVES OF NEUROLOGY, 2011, 68 (11) :1440-1446

[59]

Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model [J].

Feng, H. -L. ;

Leng, Y. ;

Ma, C. -H. ;

Zhang, J. ;

Ren, M. ;

Chuang, D. -M. .

NEUROSCIENCE, 2008, 155 (03) :567-572

[60]

Caloric Restriction Ameliorates Angiotensin II-Induced Mitochondrial Remodeling and Cardiac Hypertrophy [J].

Finckenberg, Piet ;

Eriksson, Ove ;

Baumann, Marc ;

Merasto, Saara ;

Lalowski, Maciej M. ;

Levijoki, Jouko ;

Haasio, Kristiina ;

Kyto, Ville ;

Muller, Dominik N. ;

Luft, Friedrich C. ;

Oresic, Matej ;

Mervaala, Eero .

HYPERTENSION, 2012, 59 (01) :76-U209

← 1 2 3 4 5 6 7 8 9 10 →