Discovery of In Vivo Molecular Pathways Mediating Tau-Induced Sleep and Circadian Disruption
Abstract
Disrupted daily sleep-wake cycles are prominent features of multiple neurodegenerative diseases caused by the protein Tau, collectively called tauopathies, including traumatic brain injury (TBI), frontotemporal dementia (FTD), and Alzheimer’s disease (AD). These diseases are highly prevalent especially in military populations where TBI is a major risk factor for AD. Disrupted sleep can contribute to AD, which in turn can further exacerbate poor sleep, forming a downward disease spiral. To discover new strategies to interrupt this cycle, an animal model of tauopathy has been developed that enables the discovery of new therapeutic targets that block Tau-dependent disordered sleep at an early stage prior to irreversible cell death. This innovative paradigm enables the functional screening of hundreds of individual genes for their role in mediating the toxic effects of Tau in live animals. This would be the first time that a genetic screen for human tauopathy is done using Tau-dependent behavior in animals. The identification of genes involved in Tau-dependent neuronal toxicity would provide novel insights into tauopathy disease mechanisms and aid in the development of therapeutic targets, which would benefit both military and civilian populations alike. This proposal addresses the PRMRP FY21 Topic Areas of Sleep Disorders and Restriction and Frontotemporal Degeneration.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210217
Entities
People
- Ravi Allada
Organizations
- Northwestern University
- United States Army