# Anti-inflammatory signals and neurodegeneration

> **NIH NIH R56** · SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE · 2023 · $646,104

## Abstract

Abstract
Neuroimmune signals regulate neuronal function and survival. We have strong evidence indicating that activation
of the heterodimeric interleukin-13 receptor alpha 1/interleukin-4 receptor alpha (IL-13Rα1/IL-4Rα) complex in
midbrain dopaminergic (DA) neurons affects their viability. In the brain, IL-13Rα1/IL-4Rα is uniquely expressed on
the neurons of the substantia nigra pars compacta (SNc) that are lost in Parkinson’s disease (PD). We also showed
that interleukin 13 (IL-13), produced during neuroinflammation by microglia and neurons, can modulate the
activity of dopaminergic cells and increase their susceptibility to oxidative damage. To date, there is a gap in
understanding how neuroinflammation contributes to the selective loss of DA neurons in PD. Having established
that activation of IL-13Rα1 signaling can affect the survival of dopaminergic neurons during neuroinflammation,
in the present application we wish to address this gap. Specifically, we wish to test the hypothesis that IL-13 and
neuronal IL-13Rα1 cause damage by stimulating a regulated cell death pathway called ferroptosis. We also wish
to determine to what extent IL-13 and IL-13Rα1 contribute to neurodegeneration in a mouse model of alpha-
synucleinopathy (α-Syn), a hallmark trait of PD that is associated with neuroinflammation and oxidative damage.
This will help us determine whether targeting IL-13Rα1 signaling might be a viable approach to slow
neurodegeneration in humans affected by α-synucleinopathy such as PD. The ability of ruxolitinib, an FDA-
approved drug that inhibits IL-13Rα1 signaling and that of the novel ferroptosis inhibitor CMS121, to reduce IL-
13-mediated damage in vivo will also be tested. Finally, we propose in vivo experiments un a novel mouse model
to test the hypothesis that a rare genetic variant of IL-13 found in individuals diagnosed with early-onset PD can
contribute to more rapid loss of dopaminergic neurons in a mouse with the homologue of this mutation. If
successful, these experiments will provide strong support for the hypothesis that IL-13 and IL-13Rα1 are novel
targets for preventing PD or slowing its progression, at least in a sub-set of PD patients.

## Key facts

- **NIH application ID:** 10928425
- **Project number:** 1R56NS134632-01
- **Recipient organization:** SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** BRUNO CONTI
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $646,104
- **Award type:** 1
- **Project period:** 2023-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928425

## Citation

> US National Institutes of Health, RePORTER application 10928425, Anti-inflammatory signals and neurodegeneration (1R56NS134632-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10928425. Licensed CC0.

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