RNA-Based Approach to Decrease TDP-43 Pathology and Neurotoxicity in ALS
Abstract
The aggregation of the TAR DNA binding protein (TDP-43) is the hallmark feature of ALS. TDP-43 aggregates found in the brain and spinal cord of almost all ALS patients are associated with toxicity and loss of cell viability. Our project will leverage our position as experts in TDP-43 biology and use the tools we have developed to analyze TDP-43 aggregation and inhibit this pathogenic process. We recently found that RNA molecules are potent inhibitors of TDP-43 aggregation, which leads us to ask: Can specific RNA molecules be used to prevent TDP-43 aggregation and decrease neurotoxicity? This question will be tested using our established methods using purified TDP-43, human cellular models and mouse models of ALS. Dr. Timothy Miller, the co-Principal Investigator in this proposal, and his team are experts in using RNA to reduce neurodegeneration in various models and in first-in-kind patient clinical trials. Together, our team will screen and identify new molecules to effectively reduce TDP-43 aggregation and its associated pathology.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1191066
Entities
People
- Timothy M Miller
- Yuna M Ayala
Organizations
- Saint Louis University