# Roles for astrocytic RIPK3 signaling in Parkinson's disease pathogenesis

> **NIH NIH F31** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $36,693

## Abstract

Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder of global concern, imposing an estimated cost of $52
billion per year in the United States, alone. The pathological hallmarks of PD include debilitating motor deficits,
driven by progressive degeneration of dopaminergic neurons in the nigrostriatal pathway, an essential circuit for
motor function. Emerging evidence suggests that neuroinflammation is a key player in the pathophysiology of
this degenerative process. Astrocytes are the most abundant glial cells in the central nervous system (CNS),
where they serve diverse homeostatic functions. However, following inflammatory stimulation, astrocytes enter
a reactive state that can be neurotoxic, resulting in neuronal cell death. Numerous studies have now revealed
that reactive astrocytes can contribute to clinical neurodegenerative diseases. However, the mechanism through
which homeostatic astrocytes become reactive require further investigation. The central purpose of this proposal
is to identify cellular and molecular mechanisms that promote astrocyte activation in the context of
neurodegeneration. Recent work from our laboratory and others has identified receptor-interacting protein
kinase-3 (RIPK3) as a central mediator of neuroinflammation. Here, we hypothesize that inflammatory RIPK3
signaling can induce astrocyte activation, leading to downstream neurotoxic effects and neuron loss in the
midbrain. To test this hypothesis, I will utilize novel mouse genetic systems in which RIPK3 can be specifically
deleted, overexpressed, or selectively activated in astrocytes. Studies in Aim 1 will examine how RIPK3 activity
in astrocytes shapes transcriptional and functional responses associated with neurotoxic astrocyte activation.
Aim 2 will examine whether astrocytic RIPK3 signaling can drive key molecular features of PD pathogenesis,
including dopaminergic axon degeneration and reduction of dopamine release in the striatum. Together, these
experiments aim to identify RIPK3 signaling as a vital mechanism of neurotoxic astrocyte activation and establish
roles for this pathway in the pathophysiology of PD. Identifying these cell type-specific molecular mechanisms
of Parkinsonian neurodegeneration are of vital importance for developing targeted PD therapeutics.

## Key facts

- **NIH application ID:** 10536778
- **Project number:** 1F31NS124242-01A1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Nydia Poshain Chang
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $36,693
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536778

## Citation

> US National Institutes of Health, RePORTER application 10536778, Roles for astrocytic RIPK3 signaling in Parkinson's disease pathogenesis (1F31NS124242-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10536778. Licensed CC0.

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