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

> **NIH NIH R21** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2024 · $236,850

## Abstract

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.

## Key facts

- **NIH application ID:** 10809218
- **Project number:** 1R21NS130331-01A1
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** Robert Anthony Marr
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $236,850
- **Award type:** 1
- **Project period:** 2024-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809218

## Citation

> US National Institutes of Health, RePORTER application 10809218, Pharmacological inhibition of NEP-like enzymes in traumatic brain injury and dementia (1R21NS130331-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10809218. Licensed CC0.

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