Fluvoxamine Exerts Sigma-1R to Rescue Autophagy via Pom121-Mediated Nucleocytoplasmic Transport of TFEB.

ABSTRACT: Expansion of the GGGGCC-RNA repeat is a known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which currently have no cure. Recent studies have indicated the activation of Sigma-1 receptor plays an important role in providing neuroprotection, especially in ALS and Alzheimer's disease. Nevertheless, the mechanisms underlying Sigma-1R activation and its effect on (G₄C₂)n-RNA-induced cell death remain unclear. In this study, we demonstrated that fluvoxamine is a Sigma-1R agonist that can increase chaperone activity and stabilize the protein expression of Pom121 in (G₄C₂)₃₁-RNA-expressing NSC34 cells, leading to increased colocalization at the nuclear envelope. Interestingly, fluvoxamine treatment increased

SUBMITTER: Lin CY 

PROVIDER: S-EPMC11249700 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature