Development of autophagy inducers in clinical medicine

Journal of Clinical Investigation

Volumn 125, Issue 1, 2015, Pages 14-24

  Levine, Beth ^a,b,c   Packer, Milton ^d   Codogno, Patrice ^e  

^a Center for Autophagy Research   (United States)

^b Department of Internal Medicine ^*  (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^d UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^e INSTITUT NECKER ENFANTS MALADES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS AFFECTING METABOLISM; AUTOPHAGY INDUCING AGENT; BH3 PROTEIN; CAFFEINE; CARBAMAZEPINE; CLONIDINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LITHIUM; METFORMIN; OMEGA 3 FATTY ACID; PROTEIN TYROSINE KINASE INHIBITOR; RAPAMYCIN; RESVERATROL; RILMENIDINE; SPERMIDINE; TREHALOSE; TRIFLUOPERAZINE; UNCLASSIFIED DRUG; VALPROIC ACID; VERAPAMIL; VITAMIN D;

AUTOPHAGY; CALORIC RESTRICTION; CLINICAL MEDICINE; CYTOTOXICITY; DISEASE COURSE; DISEASE SEVERITY; GENE MUTATION; HUMAN; INFECTION; METABOLIC DISORDER; NONHUMAN; REVIEW; TARGET ORGAN; UPREGULATION; ANIMAL; DRUG EFFECTS; DRUG SCREENING; GENE THERAPY; IMMUNE SYSTEM DISEASES; METABOLIC DISEASES; MUSCULAR DISEASES;

ANIMALS; AUTOPHAGY; DRUG EVALUATION, PRECLINICAL; GENETIC THERAPY; HUMANS; IMMUNE SYSTEM DISEASES; METABOLIC DISEASES; MUSCULAR DISEASES;

EID: 84920407208     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI73938     Document Type: Review

References (108)

1. Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124-131.
2. Shaid S, Brandts CH, Serve H, Dikic I. Ubiquitina-tion and selective autophagy. Cell Death Differ. 2013;20(1):21-30.
3. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107-132.
4. Hurley JH, Schulman BA. Atomistic autophagy: the structures of cellular self-digestion. Cell. 2014;157(2):300-311.
5. Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6(4):463-477.
6. Mizushima N, Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol. 2010;12(9):823-830.
7. Boya P, Reggiori F, Codogno P. Emerging regulation and functions of autophagy. Nat Cell Biol. 2013;15(7):713-720.
8. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728-741.
9. Kim KH, Lee MS. Autophagy-a key player in cellular and body metabolism. Nat Rev Endocrinol. 2014;10(6):322-337.
10. Levine B, Mizushima N, Virgin HW. Autoph-agy in immunity and inflammation. Nature. 2011;469(7330):323-325.
11. Rubinsztein DC, Marino G, Kroemer G. Autopha-gy and aging. Cell. 2011;146(5):682-695.
12. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069-1075.
13. Levine B, Kroemer G. Autophagy in the patho-genesis of disease. Cell. 2008;132(1):27-42.
14. Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368(7):651-662.
15. Jiang P, Mizushima N. Autophagy and human diseases. Cell Res. 2014;24(1):69-79.
16. Vakifahmetoglu-Norberg H, Xia H, Yuan J. Phar-macologic agents targeting autophagy. J Clin Invest. 2015;125(1):5-13.
17. Kim YC, Guan K-L. mTOR: a pharmacologic target for autophagy regulation. J Clin Invest. 2015;125(1):25-32.
18. Jiang X, Overholtzer M, Thompson CB. Autoph-agy in cellular metabolism and cancer. J Clin Invest. 2015;125(1):47-54.
19. Beau I, Mehrpour M, Codogno P. Autophago-somes and human diseases. Int J Biochem Cell Biol. 2011;43(4):460-464.
20. Sarkar S. Chemical screening platforms for autophagy drug discovery to identify therapeutic candidates for Huntington's disease and other neurodegenerative disorders. Drug Discov Today Technol. 2013;10(1):e137-e144.
21. Schneider JL, Cuervo AM. Autophagy and human disease: emerging themes. Curr Opin Genet Dev. 2014;26C:16-23.
22. Morselli E, et al. Autophagy mediates pharmacological lifespan extension by spermidine and res-veratrol. Aging (Albany NY). 2009;1(12):961-970.
23. Lonskaya I, Hebron ML, Desforges NM, Franjie A, Moussa CE. Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance. EMBO Mol Med. 2013;5(8):1247-1262.
24. Cheng Y, Ren X, Hait WN, Yang JM. Therapeutic targeting of autophagy in disease: biology and pharmacology. Pharmacol Rev. 2013;65(4):1162-1197.
25. Rubinsztein DC, Codogno P, Levine B. Autoph-agy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov. 2012;11(9):709-730.
26. Ravikumar B, et al. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat Genet. 2005;37(7):771-776.
27. Settembre C, et al. A block of autophagy in lysosomal storage disorders. Hum Mol Genet. 2008;17(1):119-129.
28. Lee JH, et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell. 2010;141(7):1146-1158.
29. Settembre C, Fraldi A, Medina DL, Ballabio A. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol. 2013;14(5):283-296.
30. Settembre C, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011; 332(6036):1429-1433.
31. Spampanato C, et al. Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol Med. 2013;5(5):691-706.
32. Maetzel D, et al. Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick Type C patient-specific iPS cells. Stem Cell Reports. 2014;2(6):866-880.
33. Sarkar S, et al. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease. Cell Rep. 2013;5(5):1302-1315.
34. Ravikumar B, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004;36(6):585-595.
35. Rose C, et al. Rilmenidine attenuates toxic-ity of polyglutamine expansions in a mouse model of Huntington's disease. Hum Mol Genet. 2010;19(11):2144-2153.
36. Hidvegi T, et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-anti-trypsin Z and reduces hepatic fibrosis. Science. 2010;329(5988):229-232.
37. Shoji-Kawata S, et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494(7436):201-206.
38. Parihar SP, et al. Statin therapy reduces the mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autoph-agy and phagosome maturation. J Infect Dis. 2014;209(5):754-763.
39. Vanhorebeek I, et al. Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. J Clin Endocrinol Metab. 2011;96(4):E633-E645.
40. Lum JJ, DeBerardinis RJ, Thompson CB. Autoph-agy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol. 2005;6(6):439-448.
41. Ryter SW, Mizumura K, Choi AM. The impact of autophagy on cell death modalities. Int J Cell Biol. 2014;2014:502676.
42. Guo JY, et al. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 2013;27(13):1447-1461.
43. Yang A, et al. Autophagy is critical for pancreatic tumor growth progression in tumors with p53 alterations. Cancer Discov. 2014;4(8):905-913.
44. Guo JY, Xia B, White E. Autophagy-mediated tumor promotion. Cell. 2013;155(6):1216-1219.
45. White E. Exploiting the bad eating habits of Ras-driven cancers. Genes Dev. 2013;27(19):2065-2071.
46. Wei Y, et al. EGFR-mediated Beclin 1 phos-phorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell. 2013;154(6):1269-1284.
47. Elgendy M, Sheridan C, Brumatti G, Martin SJ. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival. Mol Cell. 2011;42(1):23-35.
48. Rosenfeldt MT, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504(7479):296-300.
49. Rao S, et al. A dual role for autophagy in a murine model of lung cancer. Nat Commun. 2014;5:3056.
50. Shin JY, Hong SH, Kang B, Minai-Tehrani A, Cho MH. Overexpression of beclin1 induced autopha-gy and apoptosis in lungs of K-rasLA1 mice. Lung Cancer. 2013;81(3):362-370.
51. Dalby KN, Tekedereli I, Lopez-Berestein G, Ozpo-lat B. Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy. 2010;6(3):322-329.
52. Sharma K, Le N, Alotaibi M, Gewirtz DA. Cyto-toxic autophagy in cancer therapy. Int J Mol Sci. 2014;15(6):10034-10051.
53. Macintosh RL, Ryan KM. Autophagy in tumour cell death. Semin Cancer Biol. 2013;23(5):344-351.
54. Bareford MD, et al. Sorafenib enhances peme-trexed cytotoxicity through an autophagy-dependent mechanism in cancer cells. Cancer Res. 2011;71(14):4955-4967.
55. Ko A, et al. Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling. Cell Death Differ. 2014;21(1):92-99.
56. Ramirez-Peinado S, et al. Glucose-starved cells do not engage in prosurvival autophagy. J Biol Chem. 2013;288(42):30387-30398.
57. Lang MJ, et al. Glucose Starvation inhibits autoph-agy via vacuolar hydrolysis and induces plasma membrane internalization by down-regulating recycling. J Biol Chem. 2014;289(24):16736-16747.
58. Chen ZH, et al. Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema. Proc Natl Acad Sci U S A. 2010;107(44):18880-18885.
59. Sun Y, et al. Inhibition of autophagy ameliorates acute lung injury caused by avian influenza A H5N1 infection. Sci Signal. 2012;5(212):ra16.
60. Xu X, et al. Diminished autophagy limits cardiac injury in mouse models of type 1 diabetes. J Biol Chem. 2013;288(25):18077-18092.
61. Zhu H, et al. Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest. 2007;117(7):1782-1793.
62. Yin X, et al. miR-30a downregulation aggravates pressure overload-induced cardiomyocyte hypertrophy. Mol Cell Biochem. 2013;379(1-2):1-6.
63. Fujimoto K, et al. Autophagy regulates pancreatic beta cell death in response to Pdx1 deficiency and nutrient deprivation. J Biol Chem. 2009;284(40):27664-27673.
64. Wei N, et al. The involvement of autophagy pathway in exaggerated ischemic brain damage in diabetic mice. CNS Neurosci Ther. 2013;19(10):753-763.
65. Li WL, et al. The regulatory role of NF-κB in autophagy-like cell death after focal cerebral ischemia in mice. Neuroscience. 2013;244:16-30.
66. Luo CL, et al. Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience. 2011;184:54-63.
67. Liu Y, et al. Autosis is a Na+, K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc Natl Acad Sci U S A. 2013;110(51):20364-20371.
68. Matsui Y, et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res. 2007;100(6):914-922.
69. Koike M, et al. Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol. 2008;172(2):454-469.
70. Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nat Rev Immunol. 2013;13(10):722-737.
71. Alirezaei M, Flynn CT, Wood MR, Whitton JL. Pancreatic acinar cell-specific autophagy disruption reduces coxsackievirus replication and pathogen-esis in vivo. Cell Host Microbe. 2012;11(3):298-305.
72. Tian Y, Sir D, Kuo CF, Ann DK, Ou JH. Autophagy required for hepatitis B virus replication in trans-genic mice. J Virol. 2011;85(24):13453-13456.
73. Chen M, et al. Essential role for autophagy in the maintenance of immunological memory against influenza infection. Nat Med. 2014;20(5):503-510.
74. Lee HK, et al. In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity. 2010;32(2):227-239.
75. Michaud M, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 2011;334(6062):1573-1577.
76. Araki K, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460(7251):108-112.
77. Murthy A, et al. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Nature. 2014;506(7489):456-462.
78. Lassen KG, et al. Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc Natl Acad Sci U S A. 2014;111(21):7741-7746.
79. Cadwell K, et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008;456(7219):259-263.
80. Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, Yoshimori T. Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibro-blasts. J Biol Chem. 2009;284(47):32602-32609.
81. He C, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeo-stasis. Nature. 2012;481(7382):511-515.
82. Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature. 2008;454(7203):463-469.
83. Jia K, Levine B. Autophagy is required for dietary restriction-mediated life span extension in C. elegans. Autophagy. 2007;3(6):597-599.
84. Hermans G, et al. Effect of tolerating macronutri-ent deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaN-IC trial. Lancet Respir Med. 2013;1(8):621-629.
85. Watanabe T, et al. Restriction of food intake prevents postinfarction heart failure by enhancing autophagy in the surviving cardiomyocytes. Am J Pathol. 2014;184(5):1384-1394.
86. Sinha RA, et al. Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. Hepatology. 2014;59(4):1366-1380.
87. Moon JH, et al. Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy. Int J Mol Med. 2014;34(2):553-558.
88. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. N Engl J Med. 2012;366(20):1891-1904.
89. Hoyer-Hansen M, Nordbrandt SP, Jaattela M. Autophagy as a basis for the health-promoting effects of vitamin D. Trends Mol Med. 2010;16(7):295-302.
90. Hoyer-Hansen M, Bastholm L, Mathiasen IS, Elling F, Jaattela M. Vitamin D analog EB1089 triggers dramatic lysosomal changes and Beclin 1-mediated autophagic cell death. Cell Death Differ. 2005;12(10):1297-1309.
91. Campbell GR, Spector SA. Hormonally active vitamin D3 (1α, 25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection. J Biol Chem. 2011;286(21):18890-18902.
92. Campbell GR, Spector SA. Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog. 2012;8(5):e1002689.
93. Sarkar S. Regulation of autophagy by mTOR-depen-dent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers. Biochem Soc Trans. 2013;41(5):1103-1130.
94. Zhang MZ, Wang Y, Paueksakon P, Harris RC. Epidermal growth factor receptor inhibition slows progression of diabetic nephropathy in association with a decrease in endoplasmic reticulum stress and an increase in autophagy. Diabetes. 2014;63(6):2063-2072.
95. Lonskaya I, Hebron ML, Desforges NM, Schachter JB, Moussa CE. Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance. J Mol Med (Berl). 2014;92(4):373-386.
96. Le Pichon CE, et al. EGFR inhibitor erlotinib delays disease progression but does not extend survival in the SOD1 mouse model of ALS. PLoS One. 2013;8(4):e62342.
97. Wang L, et al. Epidermal growth factor receptor is a preferred target for treating amyloid-β-induced memory loss. Proc Natl Acad Sci U S A. 2012;109(41):16743-16748.
98. Conway KL, et al. Atg16l1 is required for autoph-agy in intestinal epithelial cells and protection of mice from Salmonella infection. Gastroenterol-ogy. 2013;145(6):1347-1357.
99. Sarkar S, et al. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol. 2007;3(6):331-338.
100. Zhang L, et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci U S A. 2007;104(48):19023-19028.
101. Hundeshagen P, Hamacher-Brady A, Eils R, Brady NR. Concurrent detection of autolyso-some formation and lysosomal degradation by flow cytometry in a high-content screen for inducers of autophagy. BMC Biol. 2011;9:38.
102. Rhee HW, et al. Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science. 2013;339(6125):1328-1331.
103. Wirth M, Joachim J, Tooze SA. Autophagosome formation - the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage. Semin Cancer Biol. 2013;23(5):301-309.
104. Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy. 2008;4(5):600-606.
105. Randow F, Youle RJ. Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe. 2014;15(4):403-411.
106. Wild P, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science. 2011;333(6039):228-233.
107. Korac J, et al. Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J Cell Sci. 2013;126(pt 2):580-592.
108. Varady KA, Hellerstein MK. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr. 2007;86(1):7-13.