Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications

Tyrell J. Simkins, Greg J. Duncan, Dennis Bourdette

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations


Purpose of Review: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). Inflammatory attacks in MS lead to both demyelination and axonal damage. However, due to incomplete remyelination most MS lesions remain chronically demyelinated. In parallel, there is axonal degeneration in the CNS of MS patients, contributing to progressive disability. There are currently no approved therapies that adequately restore myelin or protect axons from degeneration. In this review, we will discuss the pathophysiology of axonal loss and chronic demyelination in MS and how understanding this pathophysiology is leading to the development of new MS therapeutics. Recent Findings: Ongoing research into the function of oligodendrocytes and myelin has revealed the importance of their relationship with neuronal health. Demyelination in MS leads to a number of pathophysiologic changes contributing to axonal generation. Among these are mitochondrial dysfunction, persistent neuroinflammation, and the effects of reactive oxygen and nitrogen species. With this information, we review currently approved and investigational therapies designed to restore lost or damaged myelin and protect against neuronal degeneration. Summary: The development of therapies to restore lost myelin and protect neurons is a promising avenue of investigation for the benefit of patients with MS.

Original languageEnglish (US)
Article number26
JournalCurrent neurology and neuroscience reports
Issue number6
StatePublished - Jun 2021


  • Axonal degeneration
  • Demyelination
  • Multiple sclerosis
  • Remyelination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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