# Role of Oligodendroglia in the Pathogenesis of ALS

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $340,104

## Abstract

Project Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by
progressive degeneration of motor neurons and the eventual failure of upper and lower motor
systems. Numerous genetic mutations have been linked to ALS, but the disease mechanism
remains elusive. A large body of evidence from past studies suggests that ALS-linked, mutant-
expressing glial cells form a neurotoxic environment, and thereby play a critical role in motor
neuron degeneration and disease progression. Whereas astrocytes and microglia have been
the focus of extensive investigation as potential sources of the neurotoxicity, other glial cells
have not been given adequate consideration until recently. Oligodendrocytes, the myelinating
CNS glia, provide metabolic and nutritional support to neurons, and they undergo massive
degeneration near motor neuron cell bodies during the course of this disease. This
oligodendroglial pathology must be significant, because selective inactivation of the mutant
expression of oligodendroglia reduces disease symptoms and progression markedly more than
when the same manipulation is applied to other neural cell populations. This proposal will focus
on the cellular mechanisms of oligodendroglial dysfunction in vivo, and their detrimental impact
on motor neuron survival in mouse models of ALS. First, we will identify the relative timing and
causal relationship between oligodendrocyte degeneration and motor neuron death by
controlling the natural oligodendrocyte regeneration. Second, using newly developed, cell
specific Sod1 (G93A) expressing mice, we will define cell-intrinsic, molecular abnormalities of
oligodendrocytes and the course of disease progression after oligodendroglia-specific Sod1
(G93A) expression. Third, we will determine whether promoted oligodendrocyte regeneration
and remyelination can serve as a novel therapeutic strategy for ALS. Through these
experiments, we will investigate an important supporting glial population that previous ALS
studies have long ignored. The outcomes will determine whether the CNS myelinating glia are a
key player or a modifier in ALS, illustrate oligodendrocyte-specific molecular pathways
contributing to ALS pathophysiology, and evaluate oligodendrocyte-directed regenerative
approaches as possible ALS treatments. Through this project we will also add a novel mouse
genetic tool for cell-type specific, in vivo studies of the disease mechanisms of ALS.

## Key facts

- **NIH application ID:** 10011867
- **Project number:** 5R01NS089586-05
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Shin H Kang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,104
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011867

## Citation

> US National Institutes of Health, RePORTER application 10011867, Role of Oligodendroglia in the Pathogenesis of ALS (5R01NS089586-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10011867. Licensed CC0.

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