# RAGE: A Potential Contributor to Neuroinflammation in Amyotrophic Lateral Sclerosis

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $43,300

## Abstract

Project Summary:
Amyotrophic lateral sclerosis (ALS), an incurable, progressive, neurodegenerative disease, is characterized by
motor neuron death and neuroinflammation. In addition to direct perturbation of motor neurons, mounting
evidence suggests that activation of microglia contributes to the pathogenesis of motor neuron dysfunction and
death in this disorder. The receptor for advanced glycation end products (RAGE) contributes to neuronal and
myeloid, including microglia, dysfunction and promotes sustained inflammatory tissue-damaging responses.
Expression of RAGE ligands and RAGE increases in ALS human and murine spinal cord and previous work
illustrated that daily administration of soluble extracellular domains of RAGE, or sRAGE, which sequesters
ligands and blocks their interaction with the cell surface receptor, to Superoxide dismutase 1 (SOD1)G93A mice,
a model of familial ALS (fALS). I hypothesize that RAGE contributes to the perturbation in the ALS spinal
cord by promoting neuroinflammation and processes that ultimately lead to irrevocable loss of motor
neurons in this disorder. To test this hypothesis, my F31 grant application proposes a single aim; the work of
which is in early stages, with supporting preliminary data, at this time. (1) I will intercross Ager-floxed mice (Ager
is the gene encoding RAGE) with both SOD1G93A and Tmem119-2A-CreERT2 mice to probe the potential
contributions of microglia RAGE to ALS pathology. I have assembled all needed reagents and resources to
successfully test this hypothesis. This work will provide a model of proposed RAGE-dependent and cell-type
specific perturbations in ALS spinal cord. If successful, my work will unveil novel mechanisms of “neuro/toxic
inflammation” in ALS spinal cord and identify RAGE as a logical therapeutic target in this devastating disorder.

## Key facts

- **NIH application ID:** 10139683
- **Project number:** 1F31NS120424-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Michael MacLean
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,300
- **Award type:** 1
- **Project period:** 2020-09-18 → 2021-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139683

## Citation

> US National Institutes of Health, RePORTER application 10139683, RAGE: A Potential Contributor to Neuroinflammation in Amyotrophic Lateral Sclerosis (1F31NS120424-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10139683. Licensed CC0.

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