DELINEATING HOW EPIGENETIC REGULATION OF ACVR1C CONTRIBUTES TO AGE AND AD-RELATED MEMORY IMPAIRMENTS IN FEM…

Assistance award details

Assistance award identifier

ASST_NON_R00AG078501_075

FAIN

R00AG078501

Recipient

ARIZONA STATE UNIVERSITY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$493,019

Period

Nov 1, 2024 – Mar 31, 2028

Fiscal year

2025

Place of performance state

AZ

Source file

FY2025_All_Assistance_Full_20261006.zip

Description

DELINEATING HOW EPIGENETIC REGULATION OF ACVR1C CONTRIBUTES TO AGE AND AD-RELATED MEMORY IMPAIRMENTS IN FEMALES AND MALES - PROJECT SUMMARY (SEE INSTRUCTIONS): 15-20% OF THE US POPULATION 65+ IS PREDICTED TO BE COGNITIVELY IMPAIRED. AGE SERVES AS THE STRONGEST RISK FACTOR FOR ALZHEIMER'S DISEASE (AD) WITH 38% OF COGNITIVELY IMPAIRED OLDER ADULTS PREDICTED TO DEVELOP AD WITHIN 5 YEARS. THEREFORE, OUR ABILITY TO UNDERSTAND AND IDENTIFY MECHANISMS UNDERLYING AGE AND AD-RELATED COGNITIVE DECLINE THAT INFORM DISCOVERY OF EFFECTIVE TREATMENTS FOR IMPROVING COGNITIVE FUNCTION IS OF UTMOST IMPORTANCE. THE LONG-TERM GOAL OF THIS RESEARCH PROPOSAL IS DETERMINE WHETHER ACVR1 C FUNCTIONS AS A SELF-REGULATING MECHANISM UNDERLYING AGE AND ADRELATED IMPAIRMENTS IN COGNITIVE FUNCTION WHERE, DOWNSTREAM REGULATION BECOMES IMPAIRED WITH AGE AND AD, AND IS MAINTAINED THROUGH SELF-DIRECTED ABERRANT EPIGENETIC TRANSCRIPTIONAL REPRESSION IN THE FEMALE AND MALE BRAIN. THE PROPOSED EXPERIMENTS WILL TEST THE CENTRAL HYPOTHESIS THAT ACVR1 C REPRESENTS A KEY NOVEL MECHANISM THAT IS DISRUPTED WITH AGE AND AD AND CONTRIBUTES TO AGE AND AD-RELATED COGNITIVE DECLINE. IN THE K99 PHASE OF THIS AWARD, I FOUND THAT A MEMBER OF THE TGFR.. SIGNALING FAMILY ACVR1C, SERVES AS A BIDIRECTIONAL REGULATOR OF LONG-LASTING FORMS OF SYNAPTIC PLASTICITY AND LONG-TERM MEMORY WHICH BECOMES IMPAIRED WITH INCREASING AGE AND IN AD. OVERRIDING THIS IMPAIRMENT THROUGH OVEREXPRESSION OF ACVR1C IN THE DORSAL HIPPOCAMPUS AMELIORATES IMPAIRMENTS IN LONG TERM MEMORY AND SYNAPTIC PLASTICITY IDENTIFIED IN AGING AND 5XFAD MICE IN THE ROD PHASE, I WILL CONTINUE TO INVESTIGATE THE ROLE OF ACVR1C IN AGE AND AD-RELATED MEMORY FUNCTION. I WILL DETERMINE WHETHER ACVR1 C FUNCTIONS AS A SELF-REGULATING EPIGENETIC MECHANISM MEDIATING GENE EXPRESSION AND MEMORY IN THE ADULT, AGING AND AD FEMALE AND MALE BRAIN. TO BETTER UNDERSTAND HOW DOWNSTREAM ACVR1 C SIGNALING MAY BE CONTRIBUTING TO IMPAIRMENTS IN AGE AND AD-RELATED MEMORY FORMATION W