Neurofilament Changes in Multiple Sclerosis

A Wilkins

Research output: Chapter in Book/Report/Conference proceedingChapter in a book


Multiple sclerosis is a disease of the central nervous system characterised by episodes of neurological dysfunction which often recover, usually followed some years later by progressive and irreversible decline. Lesions of multiple sclerosis are characterised by varying degrees of inflammation, myelin and oligodendrocyte loss, astrogliosis and axonal pathology. Axonal loss is seen in progressive phases of the disease and appears to correlate well with clinical disability. Prior to loss of axons, pathological specimens have revealed changes in the immunohistochemical phenotype of axons. Specifically there may be evidence of dephosphorylation of neurofilaments within axons and transection of axons leading to the formation of axonal spheroids which are rich in dephosphorylated neurofilaments. Evidence of axonal transport defects may also be found in lesions with accumulation of amyloid precursor protein within the axon. Mechanisms of axonal pathology in multiple sclerosis remain unknown, but it is likely that inflammation causes some degree of damage in the acute phases. However there is evidence that axonal loss may continue even in the absence of inflammation. It has been postulated that axonal loss in this situation occurs due to loss of trophic support from myelin and oligodendrocytes. Oligodendrocytes and myelin are known to provide trophic support for axons and specifically can influence phosphorylated neurofilament levels. The precise mechanisms are unknown, but recent evidence suggests a combination of contact mediated and soluble factors may increase neurofilament phosphorylation and promote axonal protection. Knowledge of such mechanisms may lead to improved therapies to prevent progressive disease. This review will discuss axonal changes in multiple sclerosis, specifically alteration in neurofilament phosphorylation states, and potential mechanisms of axonal protection.
Translated title of the contributionNeurofilament Changes in Multiple Sclerosis
Original languageEnglish
Title of host publicationNew Research on Neurofilament Proteins
EditorsRK Arlen
PublisherNova Science Publishers
Number of pages0
ISBN (Print)9781600213960
Publication statusPublished - 2007

Bibliographical note

Other identifier: 1600213960


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