Transposable element activation in Alzheimer's disease and related tauopathies │Dr Bess Frost

Summary:
Transposable elements, known colloquially as ‘jumping genes’, constitute approximately 45% of the human genome. Cells utilize epigenetic defences to limit transposable element jumping, including the formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate the clearance of transposable element transcripts. We have utilized fruit flies, mice and postmortem human brain samples to identify transposable element dysregulation as a key mediator of neuronal death in tauopathies, a group of neurodegenerative disorders that are pathologically characterized by deposits of tau protein in the brain. Mechanistically, we find that heterochromatin decondensation and reduction of piwi and piRNAs drive transposable element dysregulation in tauopathy. We further report a significant increase in transcripts of the endogenous retrovirus class of transposable elements in human Alzheimer’s disease and progressive supranuclear palsy, suggesting that transposable element dysregulation is conserved in human tauopathy. Taken together, our data identify heterochromatin decondensation, piwi and piRNA depletion and consequent transposable element dysregulation as a pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.
Speaker Bio:
Dr. Bess Frost is an Assistant Professor at the Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disease, and the Department of Cell Systems and Anatomy at the University of Texas Health San Antonio. Dr Frost has been a member of the Tau Consortium since 2017. Designated as a “Rising STAR” in the University of Texas system, Dr Frost was the recipient of a 2019 Presidential Excellence Award for Junior Research Scholar from the University of Texas Health San Antonio, and a 2020 O’Donnell Award in Medicine from the Academy of Medicine, Engineering, and Science of Texas.
Dr Frost obtained her undergraduate degree from the University of Texas, Austin. She went on to earn her PhD from the University of California San Francisco in the laboratory of Dr Marc Diamond. As a graduate student, Bess pioneered work that ignited a now prominent area of research, which is that tau, a key pathological player in Alzheimer’s disease and other tauopathies, adopts prion-like characteristics that help explain its pathological spread through the brain and the diverse disease phenotypes of the human tauopathies.
Dr Frost performed her postdoctoral work at Harvard Medical School in the laboratory of Dr Mel Feany, where she identified lamin dysfunction and subsequent widespread relaxation of heterochromatic DNA as a novel mechanism whereby pathogenic forms of tau cause neuronal death in Alzheimer's disease and related tauopathies.
Dr Frost’s independent laboratory studies fundamental processes in cell biology that drive age-related neurodegenerative disorders. A major focus is on the consequences of tau-induced disruption of nuclear and genomic architecture in regard to RNA handling and transposable element activation, and development of screenable Drosophila models of protein aggregation and prion-like propagation.
Moderator:
Mahmoud Maina, University of Sussex, UK.
en.wikipedia.org/wiki/Mahmoud...
Coordinator:
Mosab Ali Awadelkareem, Al-Neelain University, Sudan.
Society of Neuroscientists of Africa - SONA:
sonafrica.org/
/ sonaorg
/ society-of-neuroscient...
/ @societyofneuroscienti...
TReND in Africa:
trendinafrica.org/
www.flickr.com/photos/trendin...
trendinafrica?lan...
/ trendinafrica
Worldwide Neuro:
www.worldwideneuro.com/
/ worldwideneuro