Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases.
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.
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, United Kingdom.
Maurizio
M
Renna
Maria
M
Jimenez-Sanchez
Sovan
S
Sarkar
David C
DC
Rubinsztein
D000818:Animals; D001343:Autophagy; D001671:Biochemistry / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D015398:Signal Transduction
D011506:Proteins