Heat shock protein amplification improves cerebellar myelination in the Npc1^nih mouse model.

ABSTRACT:

Background

Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1^nih (Npc1^-/-) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1^-/- mice. Taken together, these findings prompted the i

SUBMITTER: Gray J 

PROVIDER: S-EPMC9713282 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature