4.6 Review

Oxidized phospholipids as novel mediators of neurodegeneration

Journal

TRENDS IN NEUROSCIENCES
Volume 45, Issue 6, Pages 419-429

Publisher

CELL PRESS
DOI: 10.1016/j.tins.2022.03.002

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Funding

  1. MS Society of Canada
  2. Canadian Institutes of Health Research (CIHR) [3527, 167270]
  3. CIHR
  4. Canada Research Chair (Tier 1) program

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Neurodegeneration in neurological diseases is driven by inflammation and oxidative stress, leading to the formation of oxidized phospholipids known as OxPCs. OxPCs have been identified as biomarkers of oxidative stress and also exhibit potent neurotoxicity, which requires neutralization by microglia. Investigating OxPCs is crucial for understanding injury in neurological conditions.
Neurodegeneration drives the progression of many neurological diseases. Inflammation and oxidative stress occurring in the CNS promote lipid peroxidation, leading to the generation of oxidized phospholipids such as oxidized phosphati-dylcholines (OxPCs). OxPCs have been proposed as biomarkers of oxidative stress, where their detection in lesions in multiple sclerosis (MS), frontotemporal lobe dementia, spinal cord injury, and amyotrophic lateral sclerosis (ALS) implies that oxidative insult had occurred. However, recent findings highlight OxPCs as potent neurotoxic species requiring neutralization by microglia. Here, we summa-rize the science of OxPCs, including lessons from non-CNS diseases. We discuss the potential of OxPCs as common drivers of injury across neurological conditions and encourage investigations of OxPCs as novel neurotoxins.

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