Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases

Maurizio Renna; Maria Jimenez-Sanchez; Sovan Sarkar; David C. Rubinsztein

doi:10.1074/jbc.R109.072181

Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases

Maurizio Renna, Maria Jimenez-Sanchez, Sovan Sarkar, David C. Rubinsztein

Basic and Clinical Neuroscience

Cambridge University Hospitals NHS Foundation Trust

Research output: Contribution to journal › Short survey › peer-review

172 Citations (Scopus)

Abstract

Many of the neurodegenerative diseases that afflict people are caused by intracytoplasmic aggregate-prone proteins. These include Parkinson disease, tauopathies, and polyglutamine expansion diseases such as Huntington disease. In Mendelian forms of these diseases, the mutations generally confer toxic novel functions on the relevant proteins. Thus, one potential strategy for dealing with these mutant proteins is to enhance their degradation. This can be achieved by up-regulating macroautophagy, which we will henceforth call autophagy. In this minireview, we will consider the reasons why autophagy up-regulation may be a powerful strategy for these diseases. In addition, we will consider some of the drugs and associated signaling pathways that can be used to induce autophagy with these therapeutic aims in mind.

Original language	English
Pages (from-to)	11061-11067
Number of pages	7
Journal	Journal of Biological Chemistry
Volume	285
Issue number	15
DOIs	https://doi.org/10.1074/jbc.R109.072181
Publication status	Published - 9 Apr 2010

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AB - Many of the neurodegenerative diseases that afflict people are caused by intracytoplasmic aggregate-prone proteins. These include Parkinson disease, tauopathies, and polyglutamine expansion diseases such as Huntington disease. In Mendelian forms of these diseases, the mutations generally confer toxic novel functions on the relevant proteins. Thus, one potential strategy for dealing with these mutant proteins is to enhance their degradation. This can be achieved by up-regulating macroautophagy, which we will henceforth call autophagy. In this minireview, we will consider the reasons why autophagy up-regulation may be a powerful strategy for these diseases. In addition, we will consider some of the drugs and associated signaling pathways that can be used to induce autophagy with these therapeutic aims in mind.

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Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases

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