# Therapeutic Intervention to activate Nrf2 in Alzheimers

> **NIH NIH R21** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $198,125

## Abstract

Summary:
Alzheimer's disease (AD) is a neurodegenerative disorder that affects ever growing older population. At
present, there are no means to prevent or reverse AD. The defining clinical components of the AD are
the neuronal and synaptic loss, the accumulation of extracellular deposits of amyloid-beta (Aβ) and the
formation of intracellular neurofibrillary tangles. Evidence suggests that the presence of A is toxic, and
the mechanism of cytotoxicity involves the production of reactive oxidative stress. A master regulator of
antioxidant response is nuclear factor-erythroid 2 related factor 2 (Nrf2), which is deranged in AD. Nrf2
regulates the expression of most genes involved with the intrinsic antioxidant response, and it has been
widely reported that activation of this transcription factor has the potential to ameliorate the progression
of Alzheimer's disease. Most known activators of Nrf2 act indirectly by preventing its cytoplasmic
degradation mediated by Kelch-like ECH-associated protein 1 (Keap1). We recently found a unique
regulatory mechanism of Nrf2 at the level of protein translation and were able to create a biosensor to
detect activators of Nrf2 translation. We performed a secondary screen and were able to triage the Nrf2
translational activators to 9 molecules. Our goal now is to identify lead candidates with physiochemical
properties that meet the criteria for advancement to in vivo PK and efficacy studies. To accomplish this,
we have proposed to use a medicinal chemistry approach to generate novel non-toxic activators of Nrf2
translation.

## Key facts

- **NIH application ID:** 9851775
- **Project number:** 5R21AG061689-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** SALIM MERALI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,125
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851775

## Citation

> US National Institutes of Health, RePORTER application 9851775, Therapeutic Intervention to activate Nrf2 in Alzheimers (5R21AG061689-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851775. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*