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Does E4orf1 prevent further deterioration in Alzheimer's disease pathology in older mice

Award Number: R21AG068940
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Does E4orf1 prevent further deterioration in Alzheimer's disease pathology in older mice - PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD), is a neurodegenerative disease with associated cognitive decline, dementia and eventual death. There has been significant advancement in our understanding of AD neuropathology, however, there are no therapeutic strategies that consistently relieve cognitive symptoms or prevent, cure or slow its progression. Interestingly, a number of well-designed epidemiological studies have established a link between Type 2 Diabetes (T2D), a chronic, age-related degenerative disorder and AD, identifying T2D as a risk factor for developing all cause dementia and dementia attributable to AD. T2D and AD, together with other neurological conditions, share several clinical and biochemical features. Particularly important amongst these is impaired insulin signaling, suggesting overlapping pathogenic mechanisms. Hence, an effective treatment strategy in one disease could have potential value in the other. Several clinical and basic science studies have shown that anti-diabetic medications can improve cognitive function. Despite promise, none of these strategies have resulted in improving our understanding or effective treatment options. The long-term goal is to dissect shared mechanisms between T2D and AD regulating the molecular pathways in AD progression. These discoveries will facilitate discover effective treatment strategies to prevent AD or its progression. Previous treatment strategies either act in the periphery or directly in the brain, raising the question if peripheral as well as central glycemic control needs to be targeted for influencing AD. Therefore, the central hypothesis is that peripheral hyperinsulinemia contributes to brain insulin resistance and cognitive decline, and that alleviating hyperinsulinemia in both periphery and brain regions will reduce AD-related molecular deterioration. The overall objective of this exploratory grant is to harness the ability of adenoviral protein E4orf1 to reduce peripheral and central hyperinsulinemia and hyperglycemia to attenuate AD progression. The rationale is that restoring normal insulin action and prevention of further impairment in cognition decline will help identify mechanisms to offer new therapeutic opportunities. Using the endogenous insulin sparing action of adenoviral protein E4orf1, the aims will elucidate a previously unidentified therapeutic approach for the effective treatment of AD. This is a paradigm shift from previously used anti-diabetic approaches for AD treatment and will help modify currently available therapies or identify new options for prevention and better clinical management of AD.


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 = -$8,146 )
2026	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Aging Research	000	2	12/4/2025	NON-COMPETING CONTINUATION	-$8,146
														Subtotal = -$8,146

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Aging Research	000	2	11/2/2023	NON-COMPETING CONTINUATION	$0
2024	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Aging Research	001	2	7/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $224,407 )
2022	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Aging Research	000	2	6/10/2022	NON-COMPETING CONTINUATION	$224,407
														Subtotal = $224,407

Issue Date FY: 2021 ( Subtotal = $186,400 )
2021	2021	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Aging Research	000	1	9/20/2021	NEW	$186,400
														Subtotal = $186,400

Grand Total All Awards = $402,661

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Does E4orf1 prevent further deterioration in Alzheimer's disease pathology in older mice

Award Number: R21AG068940

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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