CELL-SPECIFIC REGULATION OF RNA DEGRADATION IN AGING AND DISEASE - PROJECT SUMMARY A GROWING NUMBER OF AMER…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
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ASST_NON_K00AG088436_075 · THE REGENTS OF THE UNIVERSITY OF CALIFORNIA · Department of Health and Human Services
Compare Multiple AI Models with SmartSoloExplore CaptureIQ IntelligenceAssistance award details
- Assistance award identifier
- ASST_NON_K00AG088436_075
- FAIN
- K00AG088436
- Recipient
- THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $83,274
- Period
- Sep 16, 2024 – May 31, 2030
- Fiscal year
- 2026
- Place of performance state
- CA
- Source file
- FY2026_All_Assistance_Full_20261006.zip
Description
CELL-SPECIFIC REGULATION OF RNA DEGRADATION IN AGING AND DISEASE - PROJECT SUMMARY A GROWING NUMBER OF AMERICANS OVER THE AGE OF 65 LIVE WITH DEMENTIA. A SET OF DEVASTATING NEURODEGENERATIVE DISEASES CAUSE DEMENTIA, INCLUDING ALZHEIMERâS DISEASE (AD) AND FRONTOTEMPORAL LOBAR DEGENERATION (FTLD). NEUROFIBRILLARY TANGLES COMPOSED OF HYPERPHOSPHORYLATED TAU ARE A PATHOLOGICAL HALLMARK OF AD AND RELATED TAUOPATHY DISORDERS INCLUDING FTLD-TAU. SEVERAL OTHER PATHOLOGIES ALSO DRIVE NEURODEGENERATION IN AD RELATED DEMENTIAS (ADRD), INCLUDING THE AGGREGATION OF THE RNA BINDING PROTEIN TDP-43 AND EXPANSION-RELATED POLYGLUTAMINE REPEAT PROTEINS (POLYQ). WHILE THE ULTIMATE MOLECULAR MECHANISMS DRIVING NEURODEGENERATION IN AD/ADRD ARE POORLY UNDERSTOOD, DISRUPTIONS TO MANY ASPECTS OF NUCLEAR HOMEOSTASIS IN NEURONS CONTRIBUTE TO THESE AGE-RELATED DISEASES, INCLUDING DISRUPTIONS TO NUCLEAR PORE COMPLEXES, NUCLEOCYTOPLASMIC TRANSPORT AND, AS I HAVE HELPED TO SHOW, NUCLEAR SPECKLES AND RNA PROCESSING. MY PUBLISHED WORK AND PRELIMINARY DATA NOW ALSO NOMINATE NUCLEAR PROTEOSTASIS AND NUCLEAR UBIQUITIN PROTEASOME SYSTEM (UPS) MACHINERY AS NOVEL AND SHARED REGULATORS OF THE EARLY PATHOGENESIS OF NEUROTOXIC AGGREGATES AND NEURODEGENERATION IN AD, FTLD, AND HUNTINGTONâS DISEASE, AN INHERITED EARLY-ONSET DEMENTIA. I PREVIOUSLY SHOWED THAT GENETIC DELETION OF SPOP HOMOLOG SPOP-1 RESCUES SIGNIFICANT BEHAVIORAL DEFICITS, PROTEIN AGGREGATION, LIFESPAN DEFECTS, AND NEURODEGENERATION DRIVEN BY THE MICROTUBULE-BINDING PROTEIN TAU IN A CAENORHABDITIS ELEGANS MODEL OF TAUOPATHY. MY PRELIMINARY EVIDENCE SUGGESTS THAT THE ACTIVITY OF C. ELEGANS SPOP-1/CUL-3 NUCLEAR SUBSTRATE BET-2, HOMOLOGOUS TO THE BROMODOMAIN AND EXTRATERMINAL DOMAIN (BET) FAMILY OF TRANSCRIPTION FACTOR PROTEINS IN HUMANS (BRD2, BRD3, BRD4, AND BRDT), UNDERLIE THESE RESULTS. MY EARLY DATA ALSO SHOW SPOP MODIFIES TDP-43 AND POLYQ NEUROTOXICITY IN MODELS OF AD/ADRD PROTEINOPATHY AND IS TRANSLATIONALLY RELEVANT IN MAMMALIAN NEURON