Exocytosis subunit regulates the toxicity in ALS
C9ORF72 gene containing GGGGCC (G4C2) repeats have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), however, how this genetic mutation leads to neurodegeneration remains unclear.
Sec5/EXOC2 is a subunit of the octameric exocyst complex. Exocysts participate in protein trafficking and spatiotemporal regulation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly for exocytosis, which is essential for neuronal function.
The researchers deleted the gene EXOC2 from patient stem cells and then differentiated them into motor neurons.
They found that several amyotrophic lateral sclerosis related phenotypes were rescued in patient neurons when EXOC2 was deleted or knocked down by EXOC2 antisense oligonucleotides.
This study identifies EXOC2 as a potential therapeutic target.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00703-4
