# The Mitochondrion-STING Axis in An Early Childhood Onset Neurodegenerative Disease

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $466,631

## Abstract

PROJECT SUMMARY
 Mitochondria are powerhouses of the cell that are often viewed as bacteria living in the cytosol. Stressed
or damaged mitochondria induce inflammation through activation of multiple innate immune signaling pathways
including the DNA sensing cGAS-STING pathway. We recently showed that deficiency of a cytoplasmic
deglycosylase NGLY1 results in mitochondrial damage and potent activation of the STING pathway. Mutations
in the NGLY1 gene are associated with an early childhood onset neurodegenetive disease with high mortality
and no therapy. We recently established and characterized a Ngly1-deficient mouse model that develop early
onset and progressive deteriorating coordination and motor functions. We also present exciting molecular and
genetic evidence that implicate the mitochondrion-STING axis in neuropathology. The overall goal of this project
is to define the neuro-pathological mechanism of NGLY1-deficiency, with a strong focus on the mechanism of
the mitochondrion-STING axis. Aim 1 will define cell type specificity through genetic and single-cell approaches.
Aim 2 will dissect intracellular signaling pathways in neuronal and glial cells. Aim 3 will evaluate therapies
targeting the mitochondrion-STING axis. Studies proposed here should reveal the central mechanism of the
mitochondrion-STING axis in neuropathology and neurodegeneration, which will have broad implications in many
complex neurogenerative diseases that are affecting millions of people.

## Key facts

- **NIH application ID:** 10297664
- **Project number:** 1R01NS117424-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Nan Yan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,631
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297664

## Citation

> US National Institutes of Health, RePORTER application 10297664, The Mitochondrion-STING Axis in An Early Childhood Onset Neurodegenerative Disease (1R01NS117424-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10297664. Licensed CC0.

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