Journal
MOLECULAR NEURODEGENERATION
Volume 17, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13024-022-00538-8
Keywords
Cuprizone; Multiple Sclerosis; Demyelination; Oligodendrocytes; Inflammation; Cell death; Astrocytes; Microglia; CNS
Categories
Funding
- Marie Sklodowska-Curie Individual Fellowship (MSCAIF)
- Banting Postdoctoral Fellowship (Canadian Institute for Health Research
- CIHR)
- CIHR
- NSERC
- University of Alberta
- Brain Canada Foundation through the Canada Brain Research fund
- Azrieli Foundation
- Health Canada
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This review provides an updated understanding of cuprizone-induced demyelination, showcasing two modes of action: intrinsic cell damage and extrinsic cellular damage. Recent developments in research on different forms of cell death induced by cuprizone are also summarized.
Background The dietary consumption of cuprizone - a copper chelator - has long been known to induce demyelination of specific brain structures and is widely used as model of multiple sclerosis. Despite the extensive use of cuprizone, the mechanism by which it induces demyelination are still unknown. With this review we provide an updated understanding of this model, by showcasing two distinct yet overlapping modes of action for cuprizone-induced demyelination; 1) damage originating from within the oligodendrocyte, caused by mitochondrial dysfunction or reduced myelin protein synthesis. We term this mode of action 'intrinsic cell damage'. And 2) damage to the oligodendrocyte exerted by inflammatory molecules, brain resident cells, such as oligodendrocytes, astrocytes, and microglia or peripheral immune cells - neutrophils or T-cells. We term this mode of action 'extrinsic cellular damage'. Lastly, we summarize recent developments in research on different forms of cell death induced by cuprizone, which could add valuable insights into the mechanisms of cuprizone toxicity. With this review we hope to provide a modern understanding of cuprizone-induced demyelination to understand the causes behind the demyelination in MS.
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