Restoration of Shal/K_V4 proteostasis and motor function in a Drosophila model of spinocerebellar ataxia type 19/22.

ABSTRACT: Loss-of-function mutations in the human KCND3 gene encoding K_V4.3 K⁺ channels are linked to the autosomal dominant neurodegenerative disease spinocerebellar ataxia type 19/22 (SCA19/22). Previous biophysical and biochemical analyses in vitro support the notion that the autosomal dominant inheritance pattern of SCA19/22 is associated with the dominant-negative effects of disease-causing K_V4.3 mutants on proteostasis of their wild-type (WT) counterpart. Herein we aimed to explore whether the disease-causing mutants might perturb protein expression of endogenous K_V4.3 channel in human cells, as well as contributing to in vivo pathomechanisms underlying motor impairments and neurodegeneration in an animal model of SCA19/22. Substantial reduction in h

SUBMITTER: Hsiao CT 

PROVIDER: S-EPMC12037467 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature