Development of autophagy inducers in clinical medicine

被引:277
作者
Levine, Beth [1 ,2 ,3 ,4 ]
Packer, Milton [5 ]
Codogno, Patrice [6 ,7 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA
[4] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA
[5] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA
[6] Univ Paris 05, Sorbonne Paris Cite, INEM, Paris, France
[7] Univ Paris 05, Sorbonne Paris Cite, INSERM U1151, CNRS UMR 8253, Paris, France
关键词
GROWTH-FACTOR RECEPTOR; LIFE-SPAN EXTENSION; CELL-DEATH; POLYGLUTAMINE EXPANSIONS; ENHANCING AUTOPHAGY; THERAPEUTIC TARGET; IMPAIRED AUTOPHAGY; HUMAN MACROPHAGES; MOUSE MODELS; INHIBITION;
D O I
10.1172/JCI73938
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Defects in autophagy have been linked to a wide range of medical illnesses, including cancer as well as infectious, neurodegenerative, inflammatory, and metabolic diseases. These observations have led to the hypothesis that autophagy inducers may prevent or treat certain clinical conditions. Lifestyle and nutritional factors, such as exercise and caloric restriction, may exert their known health benefits through the autophagy pathway. Several currently available FDA-approved drugs have been shown to enhance autophagy, and this autophagy-enhancing action may be repurposed for use in novel clinical indications. The development of new drugs that are designed to be more selective inducers of autophagy function in target organs is expected to maximize clinical benefits while minimizing toxicity. This Review summarizes the rationale and current approaches for developing autophagy inducers in medicine, the factors to be considered in defining disease targets for such therapy, and the potential benefits of such treatment for human health.
引用
收藏
页码:14 / 24
页数:11
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