Post-translational modifications of expanded polyglutamine proteins: impact on neurotoxicity
1 Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA 2 Neurogenetics Branch, NINDS, NIH, MD 20892, USA 3 Centro InterUniversitario sulle Malattie Neurodegenerative (Universita' di Firenze, Roma "Tor Vergata" e Milano) and Dipartimento di Endocrinologia, Fisiopatologia e Biologia Applicata, ‘Centro di Eccellenza per lo studio delle malattie neurodegenerative’, Università degli Studi di Milano, 20133 Milan, Italy
* To whom correspondence should be addressed. Tel: +1 2155731729; Fax: +1 2155732107; Email: pennutom{at}mail.med.upenn.edu
Received October 6, 2008; Revised October 6, 2008; Accepted December 4, 2008
Polyglutamine diseases are a family of nine neurodegenerative disorders caused by expansion in different genes of a CAG triplet repeat stretch, which encodes an elongated polyglutamine tract. This polyglutamine tract is thought to confer a toxic gain of function to the bearing proteins, which leads to late onset and progressive loss of neurons in specific regions of the central nervous system. The mechanisms underlying specificity for neuronal vulnerability remain enigmatic. One explanation is that the polyglutamine tract is not the only determinant of neurodegeneration and that protein context and post-translational events may also be crucial for pathogenesis. Here, we review how post-translational modifications of the polyglutamine proteins contribute to modulate neurotoxicity.