# Effect of Covid-19 engagement of ACE2 on brain health and pathology

> **NIH NIH P01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2021 · $196,504

## Abstract

Abstract
There are mechanisms in the brain that regulate interactions between neurons and microglial
cells and promote homeostasis. These are perturbed in several diseases including
neuropsychiatric lupus, NPSLE, studied in this PPG, and following sepsis. Many conditions of
neuroinflammation are characterized by microglial activation, and, as a consequence of this
activation, by neuronal dendritic pruning and an impaired blood brain barrier. Interestingly, a
pathway regulating homeostasis in the brain and dysregulated by neuroinflammation is the
renin-angiotensin system. Angiotensin II is generated by angiotensin converting enzyme, ACE,
and binds to a receptor AT-1 to enhance inflammation. ACE inhibitors or angiotensin receptor
blockers, ARBs, can improve neuroinflammation by either decreasing production or neutralizing
angiotensin II. In this pathway, ACE2, a membrane-bound protease, also functions to destroy
angiotensin and to generate a small angiotensin peptide, ang1-7, that is anti-inflammatory.
ACE2 is the cellular receptor for Covid-19, and binds the viral spike protein, S, more specifically,
the receptor binding domain, RBD. This study will examine the binding of S and RBD to normal
mouse brain and to mouse brain mimicking NPSLE or sepsis survival. We will further study
whether engagement by S or RBD alters the functional state of neurons, microglia and brain
endothelial cells. Finally, we ask whether the use of ACE inhibitors or ARBs alters S or RBD
binding, and whether S or RBD impair the efficacy of these medications in halting or reversing
the neurodegenerative process in NPSLE and in sepsis survivors. This study cannot be
performed in humans, but it has important translational implications.

## Key facts

- **NIH application ID:** 10151985
- **Project number:** 3P01AI073693-11A1S1
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Betty Diamond
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,504
- **Award type:** 3
- **Project period:** 2020-12-08 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151985

## Citation

> US National Institutes of Health, RePORTER application 10151985, Effect of Covid-19 engagement of ACE2 on brain health and pathology (3P01AI073693-11A1S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10151985. Licensed CC0.

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