Loss of caveolin-1 expression in knock-in mouse model of Huntington's disease suppresses pathophysiology in vivo.

ABSTRACT: Loss of cholesterol homeostasis and altered vesicle trafficking have been detected in Huntington's disease (HD) cellular and animal models, yet the role of these dysfunctions in pathophysiology of HD is unknown. We demonstrate here that defects in caveolar-related cholesterol trafficking directly contribute to the mechanism of HD in vivo. We generated new mouse models that express mutant Huntington's protein (mhtt), but have partial or total loss of caveolin-1 (Cav1) expression. Fluorescence resonance energy transfer dequenching confirms a direct interaction between mhtt and Cav1. Mhtt-expressing neurons exhibited cholesterol accumulation and suppressed caveolar-related post-Golgi trafficking from endoplasmic reticulum/Golgi to plasma membrane. Loss or reduction of Cav1 expression in a kno

SUBMITTER: Trushina E 

PROVIDER: S-EPMC3857950 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature