Polyglutamine Diseases and Neurodegeneration: The Example of Ataxin-1
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A family of nine human neurodegenerative diseases is caused by anomalous expansion of polyglutamine (polyQ) tracts in the carrier proteins. Understanding the cellular and molecular mechanisms which lead to disease is essential both for understanding these pathologies and for designing appropriate diagnostics. We review here, as a paradigmatic example, the knowledge accumulated for ataxin-1, the protein responsible for Spinocerebellar Ataxia type 1 (SCA1) and one of the smallest representatives of the polyQ family. It appears clear from this overview that understanding the properties and the interaction networks formed by both expanded and non-expanded ataxin-1 is an essential step for our comprehension of the non-pathologic function of the protein and of its role in disease. A better understanding will be reached in the future from integrating knowledge arising from different fields.
KeywordsAtaxin-1 SCA1 Neurodegenerative disease Polyglutamine CAG triplet AXH ULM Molecular switch Transcriptional repression RNA processing Protein context
We would like to thank Rajesh P. Menon and Paola Giunti for helpful comments.
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