HDAC-6 inhibition ameliorates the early neuropathology in a mouse model of Krabbe disease.

ABSTRACT:

Introduction

In Krabbe disease (KD), mutations in β-galactosylceramidase (GALC), a lysosomal enzyme responsible for the catabolism of galactolipids, leads to the accumulation of its substrates galactocerebroside and psychosine. This neurologic condition is characterized by a severe and progressive demyelination together with neuron-autonomous defects and degeneration. Twitcher mice mimic the infantile form of KD, which is the most common form of the human disease. The Twitcher CNS and PNS present demyelination, axonal loss and neuronal defects including decreased levels of acetylated tubulin, decreased microtubule stability and impaired axonal transport.

Methods

We tested whether inhibiting the α-tubulin deacetylase HDAC6 with a specific inhibitor, ACY-738, was able to count

SUBMITTER: Braz SO 

PROVIDER: S-EPMC10426153 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature