Removal of a regulatory gene called LSD1 in adult mice induces changes in gene activity that look unexpectedly like Alzheimer’s disease, scientists have discovered.
Researchers also discovered that LSD1 protein is perturbed in brain samples from humans with Alzheimer’s disease and frontotemporal dementia (FTD). Based on their findings in human patients and mice, the research team is proposing LSD1 as a central player in these neurodegenerative diseases and a drug target.
The results were published Oct. 9 in Nature Communications.
In the brain, LSD1 (lysine specific histone demethylase 1) maintains silence among genes that are supposed to be turned off. When the researchers engineered mice that have the LSD1 gene snipped out in adulthood, the mice became cognitively impaired and paralyzed. Plenty of neurons were dying in the brains of LSD1-deleted mice, although other organs seemed fine. However, they lacked aggregated proteins in their brains, like those thought to drive Alzheimer’s disease and FTD.
“In these mice, we are skipping the aggregated proteins, which are usually thought of as the triggers of dementia, and going straight to the downstream effects,” says David Katz, PhD, assistant professor of cell biology at Emory University School of Medicine. Read more