Post-translational modifications of expanded polyglutamine proteins: impact on neurotoxicity.
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.
Pennuto
Maria
M
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. pennutom@mail.med.upenn.edu
Palazzolo
Isabella
I
Poletti
Angelo
A
D000818:Animals; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine