Congratulations to Bess Frost, PhD on her publication in Trends in Neurosciences!
Dr. Frost is an Associate Professor with the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disorders, and the Department of Cell Systems and Anatomy. She is the holder/manager of the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders.
Alzheimer’s disease and related tauopathies: disorders of disrupted neuronal identity
Bess Frost
Trends in Neurosciences. 15 August 2023. doi: 10.1016/J.TINS.2023.07.006.
Abstract:
Postmitotic neurons require persistently active controls to maintain terminal differentiation. Unlike dividing cells, aberrant cell cycle activation in mature neurons causes apoptosis rather than transformation. In Alzheimer’s disease (AD) and related tauopathies, evidence suggests that pathogenic forms of tau drive neurodegeneration via neuronal cell cycle re-entry. Multiple interconnected mechanisms linking tau to cell cycle activation have been identified, including, but not limited to, tau-induced overstabilization of the actin cytoskeleton, consequent changes to nuclear architecture, and disruption of heterochromatin-mediated gene silencing. Cancer- and development-associated pathways are upregulated in human and cellular models of tauopathy, and many tau-induced cellular phenotypes are also present in various cancers and progenitor/stem cells. In this review, I delve into mechanistic parallels between tauopathies, cancer, and development, and highlight the role of tau in cancer and in the developing brain. Based on these studies, I put forth a model by which pathogenic forms of tau disrupt the program that maintains terminal neuronal differentiation, driving cell cycle re-entry and consequent neuronal death. This framework presents tauopathies as conditions involving the profound toxic disruption of neuronal identity.
Keywords: neurodegeneration; tau; cell nucleus; epigenetics; development; cancer; cell cycle