Project Grant R21AG090967

Award Date 1/1/25
Completion Date 12/31/26
Dollars Obligated $429K
Federal Grant Program
93.866
Assistance Type
Project Grant
Place of Performance
Houston, TX 77030, USA
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This Project Grant award from the National Institute on Aging's (NIA) Aging Research program (CFDA 93.866) provides $660,402 to the University of Maryland, Baltimore (UMB) to study the role of autophagy, a cellular process that recycles damaged components, in regulating lipid metabolism and inflammation in microglia during brain aging and neurodegenerative diseases like Alzheimer's disease (AD). The research aims to determine how microglial lipid phagocytosis inhibits autophagy, leading to the...
This Project Grant award from the National Institute on Aging (NIA) under the Aging Research program (CFDA 93.866) is supporting research at Yale University to investigate the role of the protein CSPα in regulating synaptic autophagy and neurodegeneration. The $461,313 award, active from June 1, 2025 to May 31, 2027, aims to elucidate the mechanisms by which CSPα maintains synaptic vesicle composition and how its deletion or mutations lead to synaptic vesicle turnover through autophagy. The...
This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $654,238 to The University of Texas Health Science Center at San Antonio to study the role of senescent cells in Alzheimer's disease and related dementias (ADRD). The primary goals are to: Identify molecular markers and changes in the microenvironment of senescent neurons compared to healthy neurons, with a focus on their contribution to neuronal death in brain aging and ADRD (R21 phase). Use...
This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $1,086,563 to The Trustees of the University of Pennsylvania to conduct research on the regulation of autophagy and lysosomal pathways in astrocytes and neurons in response to proteotoxic stress associated with alpha-synucleinopathies. The goal is to define the cell-type-specific differences in how quality control pathways are managed in neurons versus astrocytes, which may explain the increased...
This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) totaling $433,125 will fund a study to investigate the relationship between microglia, neurons, and tau pathology in Alzheimer's disease. The research will utilize a novel model system of microglial co-cultures with hippocampal assembloids derived from patient-derived induced pluripotent stem cell (iPSC) lines with MAPT mutations and healthy controls. The goal is to explore how bidirectional changes...
This $605,486 Project Grant award from the National Institute on Aging (NIA) under the Aging Research program (CFDA 93.866) supports research to define the mechanisms that coordinate late endosome and lysosome functions in neurons. The research aims to address the significant lack of understanding about how the network of proteins that control lysosome function is integrated to meet the unique demands of neurons. This is a critical barrier to understanding the relevance of abnormal lysosome...
This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) to The University of Texas Health Science Center at San Antonio provides $118,557 to study the role of SNX19 in aging brains and Alzheimer's disease (AD). The project aims to investigate the link between SNX19 expression and AD-related pathologies like neurofibrillary tangles and cognitive impairment across major brain cell types. It will also utilize human induced pluripotent stem cell-derived...
This Project Grant award of $628,000.00 from the National Institute on Aging (CFDA 93.866 - Aging Research) aims to investigate how Alzheimer's disease (AD) pathogenesis interferes with synaptic autophagy and whether targeting synaptic autophagy can be neuroprotective in an AD mouse model. The research will utilize primary hippocampal cell cultures and mouse models to determine which steps in the autophagic processing of synaptic proteins are disrupted by AD, and evaluate if overexpressing the...
This Project Grant award from the National Institute on Aging (CFDA 93.866 Aging Research) provides $1,055,313 in funding to the University of Miami to conduct research on the role of glial cells in the aging process. Specifically, the researchers will leverage C. elegans genetics and advanced imaging and supplementation methods to investigate how the glial ion channel CLH-1 controls organismal aging. The key objectives are to establish the function of glial CLH-1 in influencing aging and to...
This Project Grant award from the National Institute on Aging (NIA, CFDA 93.866 Aging Research) provides $147,486 to Albert Einstein College of Medicine to study the role of chaperone-mediated autophagy (CMA) in cellular senescence and aging. The research aims to understand: 1) how CMA activity changes upon induction of senescence, 2) if CMA modulates the kinetics of senescence and by what mechanisms, 3) if CMA is required for clearance of senescent cells by the immune system, and 4) if...

This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) aims to investigate how aging produces ultrastructural alterations to neuronal autophagy, which is critical for maintaining neuronal homeostasis and function. The $429,000 award to the University of Texas Health Science Center at Houston will be used to accomplish two specific aims over the 2-year project period starting January 1, 2025:

  1. Compare the ultrastructural features of axonal autophagic vesicles during aging using correlative light and electron microscopy (CLEM) and cryo-electron tomography (cryo-ET).

  2. Determine the ultrastructural basis for WIPI2 rescue of autophagy defects in aged neurons using live-cell imaging and cryo-ET.

The research is expected to identify stages of neuronal autophagy that could be targeted to prevent age-related cognitive decline and neurodegeneration. The findings have the potential to provide new opportunities for developing innovative therapies to address these critical health challenges associated with aging.

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