Xeroderma pigmentosum neurodegeneration multiomics using an induced pluripotent stem cell system
The mechanism of neurodegeneration in xeroderma pigmentosum (XP) is unknown.
The researchers investigated neurodegeneration in XP using induced pluripotent stem cell models, performing multi-omics over a neuronal-directed differentiation time course.
They found evidence of ER stress and marked oxidative DNA damage in XP neurons.
Interestingly, inappropriate downregulation of the ubiquitin proteasome system (UPS) distinguished XP patients who developed neurodegeneration. They show that chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00571-0
