In Drosophila, the loss of Frataxin causes iron accumulation in the nervous system, which in turn enhances sphingolipid synthesis and activation of PDK1 and Mef2, which leads to neurodegeneration.
Vijayendran Chandran, Kun Gao ... Daniel H Geschwind
Restoration of endogenous frataxin levels reverses neurologic and cardiac phenotypes associated with Friedreich's ataxia in adult mice even after significant motor dysfunction.
Cristian A Lasagna-Reeves, Maxime WC Rousseaux ... Huda Y Zoghbi
Studies in a mouse model of spinocerebellar ataxia type 1 show that a protein called capicua stabilizes toxic ataxin-1 oligomers offering a possible explanation for regional patterns of neurodegeneration.
Pathogenesis in Spinocerebellar Ataxia Type 3 is enhanced by the heat-shock protein family member, Hsc70-4, uncovering new mechanisms of toxicity for this disease and suggesting pleiotropic roles for chaperones.
Cristian A Lasagna-Reeves, Maxime WC Rousseaux ... Huda Y Zoghbi
Building on previous work (Lasagna-Reeves et al., 2015) it is shown that polyglutamine ATXN1 oligomers propagate locally in SCA1 mice, and that passive immunotherapy targeting soluble oligomers can lead to an improvement in motor coordination and a modest increase in life span.