FUNCTION OF REACTIVE ASTROCYTES IN AGING AND NEURODEGENERATIVE DISEASE - REACTIVE ASTROCYTES (RAS) ARE A FE…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG068523_075
- FAIN
- K00AG068523
- Recipient
- BRIGHAM & WOMENS HOSPITAL INC
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $352,469
- Period
- Sep 1, 2020 – Aug 31, 2025
- Fiscal year
- 2021
- Place of performance state
- MA
- Source file
- FY2021_All_Assistance_Full_20261006.zip
Description
FUNCTION OF REACTIVE ASTROCYTES IN AGING AND NEURODEGENERATIVE DISEASE - REACTIVE ASTROCYTES (RAS) ARE A FEATURE OF NORMAL AGING AND NEURODEGENERATION OF VARYING ETIOLOGIES, SUGGESTING A POTENTIAL COMMON MECHANISM. HOWEVER, THE ROLE OF RAS IN NEURODEGENERATION IS COMPLEX BECAUSE THEY CAN BE TRIGGERED BY MANY DIFFERENT STIMULI AND CAN HAVE BOTH BENEFICIAL AND HARMFUL EFFECTS TO THE CENTRAL NERVOUS SYSTEM (CNS). THUS, A BETTER UNDERSTANDING OF THE CAUSES AND FUNCTIONS OF DIFFERENT REACTIVE ASTROCYTES IS NECESSARY TO DESIGN THERAPEUTICS THAT CAN SELECTIVELY BOLSTER PROTECTIVE FUNCTIONS AND INHIBIT TOXIC EFFECTS. THERE IS ALSO A VITAL NEED TO EXPAND THE TOOLS AVAILABLE TO GENERATE REACTIVE ASTROCYTES AND TO DESCRIBE DIVERSE REACTIVE ASTROCYTE FUNCTIONS. THE LONG-TERM RESEARCH GOAL OF THIS APPLICATION IS TO GAIN DEEP MECHANISTIC UNDERSTANDING OF THE FACTORS THAT ELICIT REACTIVE ASTROCYTES AND THE FUNCTIONS OF DIFFERENT TYPES OF REACTIVE ASTROCYTES. FOR THE K00 PHASE, THE FORMATION AND THE ROLE OF RAS IN ALZHEIMERâS DISEASE (AD) AND AGING WILL BE INTERROGATED IN THE LAB OF DR. MEL FEANY. DRAMATIC CHANGES IN THE EXTRACELLULAR MATRIX (ECM) AND BRAIN STIFFNESS ARE OBSERVED IN VARIOUS CNS INJURIES, INCLUDING ALZHEIMERâS DISEASE (AD), CANCER, AND AGING. HOWEVER, WHILE GROWING ASTROCYTES ON STIFF SUBSTRATES IS KNOWN TO PROMOTE A REACTIVE ASTROCYTE PHENOTYPE, THE PHYSIOLOGICAL EFFECTS OF MECHANICALLY ACTIVATED ASTROCYTES HAVE NOT BEEN EXPLORED. IN AIM 1, A NOVEL MODEL WILL BE DEVELOPED TO STUDY RAS BY CULTURING IPSCASTROCYTES ON SUBSTRATES OF DIFFERENT STIFFNESS TO UNDERSTAND THE EFFECTS OF MECHANICAL CHANGES ON ASTROCYTES. THIS MODEL WILL BE UTILIZED TO EXAMINE POTENTIAL MECHANISMS OF RA-INDUCED TOXICITY. PROTEOGLYCANS (PGS) ARE AMONG THE MOST HIGHLY UPREGULATED GENES IN AGING AND RAS. PRELIMINARY DATA FROM DR. FEANYâS LAB IDENTIFIED GENETIC INTERACTIONS BETWEEN PGS AND MODELS OF NEURODEGENERATION IN THE FLY. I HYPOTHESIZE THAT RAS PRODUCE AN IMBALANCE OF PGS IN THE ECM,