FTD Basic Mechanisms: Characterize TDP-43 and FUS roles in FTD (Milestone 2.P)
Timeline Start - End2016 - 2025
Research Implementation AreaResearch on Disease Mechanisms
AD-Related Dementias Focus
Determine the mechanism of TDP-43 and FUS pathogenesis and toxicity.
Support research to identify the predominant mechanism(s) of TDP-43 and FUS-related pathogenesis and neurodegeneration in FTD.
Determine if and how aggregated TDP-43 spreads.
Summary of Key Accomplishments
Abnormal clumps of the proteins TDP-43 and FUS are a hallmark of FTD, ALS and related neurodegenerative diseases. Ongoing NIH-funded projects are providing new insights into how these aggregates form. For example, recent studies have shown that TDP-43 forms droplets inside cells that are prone to turn into a gel or solid during times of cellular stress. Other studies have shown that defects in the cell nucleus lead to TDP-43 and FUS dysfunction, ultimately resulting in neuronal death. Novel possible targets for therapeutic intervention in FTD and FTD-ALS are emerging from this research.
The key accomplishments summary is current as of July 2022.
- RFA-NS-18-015: Structural Biology of Alzheimer's Disease Related Dementias (ADRDs) Proteinopathies (U01)
- PAS-19-392: Small Research Grant Program for the Next Generation of Researchers in AD/ADRD: Area of Focus Basic Science (R03)
- RFA-NS-20-005: Mechanistic Basis of TDP-43-Dependent Pathobiology in Common Dementias (R01)
- RFA-NS-21-003 –Center without Walls for Mechanisms of Neurodegeneration in Frontotemporal Dementia (FTD)
- RFA-NS-21-003: Center without Walls for Mechanisms of Neurodegeneration in Frontotemporal Dementia (FTD) (U54 Clinical Trial Not Allowed)
- RFA-NS-21-006: Mechanisms of Pathological Spread of Abnormal Proteins in LBD and FTD (R01 Clinical Trial Not Allowed)
- RFA-NS-21-007: Mechanisms of Selective Vulnerability in LBD and FTD (R01 Clinical Trial Not Allowed)
Research Programs and Resources
- Structural Biology of Alzheimer's Disease Related Dementias (ADRDs) Proteinopathies
- National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD)
- NINDS Human Biomarkers Biospecimen and Data Repository (BioSEND)
- NINDS Human Cell and Data Repository (NHCDR)
- Keystone Symposium: Neurodegenerative Diseases: New Insights and Therapeutic Opportunities (Z2)
- Select projects funded in FY21
- Select projects funded in FY22
- 2016 ADRD Summit: Frontotemporal Lobar Degeneration (FTD) Focus Area 1: Basic Science: Pathogenesis and Toxicity, Recommendation 3