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

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.

• Authors: Maurizio Renna, Maria Jimenez-Sanchez, Sovan Sarkar, David C Rubinsztein
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 15 Pg. 11061-7 (Apr 09 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 20147746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Proteins

Topics

• Animals
• Autophagy
• Biochemistry (methods)
• Cytoplasm (metabolism)
• Gene Expression Regulation
• Humans
• Macrophages (metabolism)
• Models, Biological
• Mutation
• Neurodegenerative Diseases (metabolism, pathology)
• Protein Binding
• Protein Denaturation
• Protein Folding
• Proteins (chemistry)
• Signal Transduction