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Pharmacological inhibition of NEP-like enzymes in traumatic brain injury and dementia

Award Number: R21NS130331
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Pharmacological inhibition of NEP-like enzymes in traumatic brain injury and dementia - ABSTRACT Recently, my laboratory has found that the NEP-like endopeptidases, neprilysin (NEP) and NEP2, have a role in acute recovery after traumatic brain injury (TBI). This has interesting and exciting implications for the TBI field as well as for understanding risk factors for developing dementia. The causal links between TBI and dementia are becoming better understood. Many of the pathological hallmarks of Alzheimer’s disease (AD) are shared with early changes in TBI. Of note are the rapid elevations of the amyloid-beta (Aβ) peptide after TBI. Natural mechanisms of clearance of Aβ are important in slowing the progression of AD and so these clearance mechanisms may also be important in TBI. Both NEP and its homolog NEP2 degrade Aβ and are important for controlling cerebral levels of the peptide. We propose a role for these enzymes in the processes following TBI. To further investigate the role(s) of NEP/NEP2 in TBI we will use our APP humanized transgenic mice and alter the activity of these enzymes in a TBI context in both short (aim 1) and long-term (aim 2) assessments. This project will determine the importance of NEP-like enzymes in the acute pathology post TBI as well as in the development dementia.


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: 2025 ( Subtotal = $197,375 )
2025	2025	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/1/2025	NON-COMPETING CONTINUATION	$197,375
														Subtotal = $197,375

Issue Date FY: 2024 ( Subtotal = $236,850 )
2024	2024	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/13/2024	NEW	$236,850
														Subtotal = $236,850

Grand Total All Awards = $434,225

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Pharmacological inhibition of NEP-like enzymes in traumatic brain injury and dementia

Award Number: R21NS130331

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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