Mutated sigma-1R disrupts cell homeostasis in dHMN patient cells.

ABSTRACT: Hereditary-Motor-Neuropathies (dHMNs) are clinically and genetically heterogeneous neurological disorders characterized by degeneration of peripheral motoneurons. We previously identified two sigma-1 receptor (Sigma-1R) variants (p.E138Q; p.E150K) in dHMN Italian patients that behave as "loss-of-function" mutations in neuroblastoma cell lines. Here, we characterize the functional effects of Sigma-1R mutation in primary fibroblasts from homozygous patients bearing the E150K mutation, and matched controls, by performing biochemical, gene expression, immunofluorescence and Ca²⁺ imaging analysis. Our results show that Sigma-1R expression and distribution is significantly altered in patient fibroblasts. Moreover, patient cells present a general derangement of cell homeostasis as reve

SUBMITTER: Zanin S 

PROVIDER: S-EPMC11981993 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature