PLX322292

GSE98875: LSD1 inhibition induces neurodegeneration and provides a common link to Alzheimer's disease and Frontotemporal dementia

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Alzheimers disease (AD) and Frontotemporal dementia (FTD) are the two most common forms of dementia that occur during aging. Both AD and FTD are associated with the pathological aggregation of proteins. Nevertheless, it remains unclear how these protein aggregates lead to neuronal cell death in these dementias. Here we show that the histone demethylase LSD1 is mislocalized with cytoplasmic aggregates in human cases of AD and FTD. In addition, loss of LSD1 systemically in adult mice is sufficient to recapitulate many aspects of these diseases. From these data, we propose that the aggregation of Tau and TDP-43 lead to neuronal cell death in AD and FTD by interfering with the continuous requirement for LSD1 to repress inappropriate transcription. Furthermore, we observe the inappropriate reactivation of stem cell loci in the hippocampal neurons of LSD1 mutant mice. This suggests that LSD1 may function to maintain the fate of differentiated neurons by repressing stem cell transcription. SOURCE: Benjamin,G,Barwick (benjamin.barwick@emory.edu) - Boise and Vertino Labs Emory University