Characterization of small fiber pathology in a mouse model of Fabry disease.

ABSTRACT: Fabry disease (FD) is a life-threatening X-linked lysosomal storage disorder caused by α-galactosidase A (α-GAL) deficiency. Small fiber pathology and pain are major FD symptoms of unknown pathophysiology. α-GAL deficient mice (GLA KO) age-dependently accumulate globotriaosylceramide (Gb3) in dorsal root ganglion (DRG) neurons paralleled by endoplasmic stress and apoptosis as contributors to skin denervation. Old GLA KO mice show increased TRPV1 protein in DRG neurons and heat hypersensitivity upon i.pl. capsaicin. In turn, GLA KO mice are protected from heat and mechanical hypersensitivity in neuropathic and inflammatory pain models based on reduced neuronal I_h and Na_v1.7 currents. We show that in vitro α-GAL silencing increases intracellular Gb3 accumulation paralle

SUBMITTER: Hofmann L 

PROVIDER: S-EPMC6255391 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature