Development of autophagy inducers in clinical medicine
Beth Levine, … , Milton Packer, Patrice Codogno
Beth Levine, … , Milton Packer, Patrice Codogno
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):14-24. https://doi.org/10.1172/JCI73938.
View: Text | PDF
Review

Development of autophagy inducers in clinical medicine

Abstract

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.

Authors

Beth Levine, Milton Packer, Patrice Codogno

×

Figure 1

Schematic illustration of potential mechanisms by which autophagy-inducing agents may exert beneficial effects in clinical disease.

Options: View larger image (or click on image) Download as PowerPoint
Schematic illustration of potential mechanisms by which autophagy-induci...
The precise mechanisms underlying the beneficial effects of autophagy upregulation in preventing or treating different diseases are not fully understood, and multiple different functions of the autophagy pathway or of specific autophagy proteins (acting independently of autophagy) are likely to be contributory. The mechanisms and target diseases shown are representative examples based on animal studies and human genetic data (see Tables 1–3). Other functions of autophagy and autophagy proteins not depicted here may be important, and other diseases not listed here may be targets for autophagy induction.