Targeting mislocalization of nucleic acids in Alzheimer’s disease and frontotemporal dementia
The researchers demonstrate that mutations in APP, PSEN1, and VCP disrupt mRNA nucleocytoplasmic distribution in human iPSC-derived cortical neurons derived from familial AD and FTD.
The authors also show redistribution of mitochondria-related transcripts across AD and FTD neurons. In addition,they found abnormal cytoplasmic accumulation of mtDNA in AD and FTD cortical neurons together with evidence of mitochondrial aberrance.
Pharmacological inhibition of the VCP D2 ATPase domain restores proper mRNA localization, highlighting a potential therapeutic avenue for neurodegenerative diseases.
https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00638-2
https://sciencemission.com/Mislocalization-of-nucleic-acids-in-AZ-and-FTD
