Dr. Huda Zoghbi's lab recently published an exciting
paper in Cell (Lam et al., Cell 127:1335-1347, 2006) in which they showed that
Ataxin-1 (the protein containing an expanded glutamine tract in the
neurodegenerative disease, SCA1) interacts with the transcriptional repressor
Capicua in the cerebellum. Importantly, the author demonstrated that
glutamine-expanded Ataxin-1 incorporates into its native complexes just like
its wild-type counterpart and that it has to be in the native complex to cause
neurotoxicity. This finding has implications for a large host of
neurodegenerative disorders caused by gain-of-function mechanism.
A new paper from the Zoghbi lab revealed that a genetic duplication elevating
the levels of an Ataxin-1 paralog (Ataxin-1Like) suppresses the
neurodegeneration induced by glutamine-expanded Ataxin-1 in a mouse model for
the neurodegenerative disease, SCA1. Ataxin-1Like suppresses the toxicity of
Ataxin-1 by displacing it from its native stable protein complexes (Bowman et
al., Nature Genetics, in press). This finding highlights the important role of
protein paralogs in the study of neurodegenerative diseases including Alzheimer
and Parkinson diseases.
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