PerspectiveCell Biology

Cholesterol crystals impede nerve repair

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Science  09 Feb 2018:
Vol. 359, Issue 6376, pp. 635-636
DOI: 10.1126/science.aar7369

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Damage to the myelin sheath that surrounds nerve axons represents the pathological hallmark of the neurological disorder multiple sclerosis (MS) and is thought to contribute to a number of other nervous system maladies (1). Remyelination, a regenerative process that forms new myelin sheaths around demyelinated axons, restores nerve function and reverses the clinical manifestations associated with demyelination (2). Although remyelination occurs efficiently in young individuals, this restorative process proceeds less well with age (2). Inefficient remyelination results in axonal loss and progressive worsening of neurological symptoms. On page 684 of this issue, Cantuti-Castelvetri et al. (3) report that insufficient clearance (phagocytosis) of damaged myelin by aged macrophages results in the accumulation of cholesterol crystals in these cells, which elicits a maladaptive inflammatory response that is associated with impaired remyelination. Understanding this process may reveal new therapeutic opportunities for MS and other demyelinating disorders.