Related Experiment Video

Updated: Jun 13, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
09:41

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

Published on: July 19, 2019

11.7K

Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurodegeneration and are neutralized by

Yifei Dong1, Charlotte D'Mello1, William Pinsky2

  • 1Hotchkiss Brain Institute and the Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.

Nature Neuroscience
|February 19, 2021
PubMed

Insights

Oxidized phosphatidylcholines (OxPCs) in multiple sclerosis (MS) lesions drive neurodegeneration. Microglia, particularly TREM2-expressing subsets, can clear OxPCs, suggesting a therapeutic target for MS neuroprotection.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Neurodegeneration is a key driver of disability progression in multiple sclerosis (MS).
  • Oxidative stress is implicated in MS pathogenesis, with oxidized phosphatidylcholines (OxPCs) identified as markers in MS lesions.
  • Understanding the specific mechanisms driving neurodegeneration is crucial for developing effective MS therapies.

Purpose of the Study:

  • To investigate the role of oxidized phosphatidylcholines (OxPCs) in driving neurodegeneration in multiple sclerosis (MS).
  • To explore the involvement of microglia and the TREM2 pathway in response to OxPCs in MS lesions.

Main Methods:

  • In vitro studies using cultured neurons and oligodendrocytes exposed to OxPCs.
  • In vivo studies involving OxPC injection into mouse spinal cords to induce lesions.
  • Single-cell RNA sequencing to analyze microglial responses.
  • Assessment of TREM2 expression in human MS lesions and in genetically modified mice.

Main Results:

  • Oxidized phosphatidylcholines (OxPCs) directly caused neurodegeneration in cultured neurons and oligodendrocytes.
  • OxPC injection in mice induced demyelinating lesions with significant axonal loss.
  • Microglia mitigated OxPC-induced neurotoxicity, while their depletion exacerbated it.
  • Single-cell RNA sequencing revealed TREM2-high microglia subsets responding to OxPC deposition.
  • TREM2 deficiency worsened OxPC-induced lesions, and TREM2 was present in human MS lesions.

Conclusions:

  • Oxidized phosphatidylcholines (OxPCs) are potent neurotoxins contributing to neurodegeneration in MS.
  • Microglia play a protective role by clearing OxPCs, with TREM2 being a key mediator.
  • Targeting microglia-mediated OxPC clearance via TREM2 represents a potential therapeutic strategy for preventing neurodegeneration in MS.

More Related Videos

A Stably Established Two-Point Injection of Lysophosphatidylcholine-Induced Focal Demyelination Model in Mice04:55

A Stably Established Two-Point Injection of Lysophosphatidylcholine-Induced Focal Demyelination Model in Mice

Published on: May 11, 2022

4.3K
Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation08:34

Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation

Published on: June 17, 2025

691

Related Concept Videos

Parkinson's Disease: Overview01:15

Parkinson's Disease: Overview

Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is to...
Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...