Tuesday, December 2, 2025 12/2/2025

Calcium signaling and autophagy defects in Alzheimer's disease neurons

Award Number: R01AG090542
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2029

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Calcium signaling and autophagy defects in Alzheimer's disease neurons - ABSTRACT The broad, long-term objective of this grant application is to understand the mechanisms responsible for autophagy defects in neurons affected by Alzheimer’s disease (AD). Dysregulation of neuronal autophagy play important role in AD pathogenesis from the studies of both AD patients and animal models. Dysfunctional calcium (Ca2+) signaling is also a well-established driver of AD pathology. Based on results recently obtained by our laboratory we proposed a model that casually connects dysregulation of neuronal Ca2+, impaired autophagy and AD pathology. The main aim of this grant proposal is to test this novel hypothesis. To test this hypothesis, we will perform experiments with transgenic AD mouse model and will evaluate effects of (1) clinically relevant ryanodine receptor type 2 (RyanR2) inhibitors; (2) positive allosteric modulators of the sarco- endoplasmic reticulum calcium ATPase (SERCA); (3) dominant-negative constructs targeting Serine/Threonine kinase 11 interacting protein (STK11IP). In our measurements we quantify ability of these manipulations to rescue defects in neuronal autophagy and to exert synaptoprotective and neuroprotective effects. Results obtained in the proposed studies will provide essential information regarding connection between Ca2+ signaling and autophagy defects and AD, help to validate novel therapeutic targets for AD treatment and also provide information about potential lead molecules for development of AD therapeutic agents.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $650,911 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	2	11/25/2025	NON-COMPETING CONTINUATION	$650,911
														Subtotal = $650,911

Issue Date FY: 2025 ( Subtotal = $749,030 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	1	12/16/2024	NEW	$749,030
														Subtotal = $749,030

Grand Total All Awards = $1,399,941

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Calcium signaling and autophagy defects in Alzheimer's disease neurons

Award Number: R01AG090542

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/15/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2029

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