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.
David Katz, PhD
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
Emory cell biologist David Katz’s lab has facilitated a collaboration with our neighbors at Oglethorpe University, working with undergraduates on the worm C. elegans and contributing to Alzheimer’s/frontotemporal dementia research. A new article from Oglethorpe describes how C. elegans is ideal for undergraduate biology instruction. Check it out.
In the photo: Oglethorpe student and Katz lab intern Caitlin May, Oglethorpe biology professor Karen Schmeichel, Elias Castro — also an Oglethorpe student and Katz lab intern, Katz lab postdoc Teresa Lee and David Katz.
Posted on May 9, 2017
In ancient Greek mythology, the souls of the dead were made to drink from the river Lethe, so that they would forget their past lives. Something analogous happens to genes at the very beginning of life. Right after fertilization, the embryo instructs them to forget what it was like in the egg or sperm where they had come from.
This is part of the “maternal-to-zygote transition”: much of the epigenetic information carried on and around the DNA is wiped clean, so that the embryo can start from a clean slate.
Developmental biologist Lewis Wolpert once said: “It is not birth, marriage or death which is
the most important time in your life, but gastrulation,” referring to when the early embryo separates into layers of cells that eventually make up all the organs. Well, the MZT, which occurs first, comes pretty close in importance.
When this process of epigenetic reprogramming is disrupted, the consequences are often lethal. Emory cell biologists David Katz and Jadiel Wasson discovered that when mouse eggs are missing an enzyme that is critical for the MZT, on the rare instances when the mice survive to adulthood, they display odd repetitive behaviors. Read more
Earlier today, weÂ posted a notice on Eurekalert for a Sunday, December 13 presentation by graduate student Jessica Konen at theÂ American Society for Cell Biology meeting in San Diego.
Her research, performed with Adam Marcus at Winship Cancer Institute, was the topic of a video that recently won first prize in a contest sponsored by the Association of American Medical Colleges. ThisÂ was our video team’s first use of theÂ “fast hand on whiteboard” effect, and a lot of fun to make. The video’s strength growsÂ out of the footageÂ Konen and Marcus have of cancer cells migrating in culture. Check it out, if you haven’t already.
PosterÂ presentations at the 2015 ASCB meeting can be found by searching this PDF. A few Emory-centric highlights:
*Chelsey Ruppersburg and Criss Hartzell’s work on the “nimbus”, a torus-shaped structure enriched in proteins needed to build the cell’s primary cilium
*Anita CorbettÂ on how Emory students have a strong record of attaining their own NIH research funding
*Additional work by Adam Marcus’ lab on the tumor suppressor gene LKB1 and how its loss drives lung cancer cells to take on a “unique amoeboid morphology”
*Research from David Katz’s lab on the “epigenetic eraser” LSD1 (lysine-specific demethylase) and its function in neurons and neurodegeneration Read more