Pathogenic SREK1 decrease in Huntington’s disease and the resulting deficit in TAF1 could be a mechanism for striatal neurodegeneration and a target for therapeutic intervention.
Why this matters
SRSF6 activity in the striatum is altered in patients with Huntington’s disease. SREK1 is a direct interactor and regulator of SRSF6, as well TAF1. Reduced TAF1 expression due to a retrotransposon insertion mutation causes X-linked dystonia parkinsonism, similar to Huntington’s disease.
The results of this study indicate reduced SREK1 lead to a reduction in TAF1 levels, which can be rescued by overexpression of SREK1. In mice models, overexpression of SREK1 also attenuated the motor coordination deficit associated with Huntington’s disease. Together, the findings of this study implicate decreased SREK1 expression, and the resulting deficit in TAF1, in the pathogenesis of Huntington’s disease. This is evidence of a mechanistic convergence with X-linked dystonia parkinsonism and poses new targets for therapeutic intervention.