# Mechanism of alpha5 integrin contribution to Amyotrophic Lateral Sclerosis pathology.

> **NIH NS R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2026 · $615,186

## Abstract

Project Summary/Abstract
Amyotrophic Lateral Sclerosis (ALS) is the third most common neurodegenerative disease, with no cure and
limited treatment options. While motor neurons are primarily affected, non-neuronal cells, particularly myeloid
cells (microglia and peripheral macrophages), significantly influence disease progression. Our preliminary
studies identified α5 integrin as a novel molecular switch that emerges in myeloid cells during ALS progression
and correlates with inflammatory states in both familial and sporadic ALS patients. Importantly, blocking α5
integrin significantly extends survival in ALS mouse models. This proposal aims to define the mechanistic role
of α5 integrin in ALS pathogenesis through two specific aims: 1) Define the cell type-specific contributions of
α5 integrin in ALS pathogenesis using conditional knockout models to selectively delete α5 integrin in microglia
and/or peripheral macrophages, and 2) Elucidate how α5 integrin regulates microglial function in ALS
pathology using human iPSC-derived cellular systems. We hypothesize that α5 integrin functions as a critical
molecular switch driving the transition of myeloid cells from homeostatic to disease-associated microglia (DAM)
states in ALS. By combining genetic models with human iPSC-derived cellular systems, we will determine how
α5 integrin influences microglial migration, phagocytosis, and interactions with motor neurons in both healthy
and ALS contexts. This study represents the first comprehensive investigation of α5 integrin's role in myeloid
cell function in ALS. Our preliminary data suggests that targeting α5 integrin represents a novel therapeutic
strategy to modulate and slow disease progression. By elucidating the molecular mechanisms governing
myeloid cell contributions to ALS pathology, we will pave the way for more effective immunomodulatory
treatments for this devastating disease.

## Key facts

- **NIH application ID:** 11279775
- **Project number:** 1R01NS146509-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Bahareh  Ajami
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $615,186
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11279775

## Citation

> US National Institutes of Health, RePORTER application 11279775, Mechanism of alpha5 integrin contribution to Amyotrophic Lateral Sclerosis pathology. (1R01NS146509-01). Retrieved via AI Analytics 2026-05-18 from https://api.ai-analytics.org/grant/nih/11279775. Licensed CC0.

---

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