Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia.

ABSTRACT: Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. HSPs are characterized by lower-extremity weakness and spasticity. However, there is no specific clinical treatment strategy to prevent or reverse nerve degeneration in HSPs. Mutations in receptor expression-enhancing protein 1 (REEP1) are well-recognized and relatively common causes of autosomal dominant HSPs. REEP1 modifies the endoplasmic reticulum (ER) shape, and is implicated in the ER stress response. Defects in the ER stress response seem to be crucial mechanisms underlying HSP neurodegeneration. Here, we report that REEP1-/- mice exhibit progressive motor deficits, along with denervation of neuromuscular junctions and increased ER stress. Moreover, marked axonal degeneration and morphological abnormalitie

SUBMITTER: Wang B 

PROVIDER: S-EPMC7541344 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature