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Neurofilament Changes in Multiple Sclerosis

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Cytoskeleton of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 3))

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Abstract

Multiple sclerosis is a disease of the central nervous system usually characterised by relapsing episodes of neurological dysfunction, often 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 inflammation in the acute disease phases is likely to cause significant damage. There is also 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 chapter will discuss axonal changes in multiple sclerosis, specifically alterations in neurofilament phosphorylation states, and potential mechanisms of axonal protection.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

CNPase:

2′,3′-Cyclic nucleotide 3′-phosphodiesterase

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

GDNF:

Glial cell-line derived neurotrophic factor

IF:

Intermediate filament

IGF-1:

Insulin-like growth factor type-1

MAG:

Myelin associated glycoprotein

MBP:

Myelin basic protein

MOG:

Myelin-oligodendrocyte glycoprotein

NF:

Neurofilament

NGF:

Nerve growth factor

NO:

Nitric oxide

PLP:

Proteolipid protein

ROS:

Reactive oxygen species

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Acknowledgment

EG is supported by a Junior Fellowship from the Multiple Sclerosis Society (UK).

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  1. Department of Neurology, Institute of Clinical Neurosciences, Clinical Sciences North Bristol, University of Bristol, Bristol, BS8 1TH, UK

    Elizabeth Gray & Alastair Wilkins

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  1. Psychiatric Research, Nathan S. Kline Institute for, 140 Old Orangeburg Road, Orangeburg, 10962, New York, USA

    Ralph A. Nixon

  2. Psychiatric Research, Nathan S. Kline Institute for, 140 Old Orangeburg Road, Orangeburg, 10962, New York, USA

    Aidong Yuan

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Gray, E., Wilkins, A. (2011). Neurofilament Changes in Multiple Sclerosis. In: Nixon, R., Yuan, A. (eds) Cytoskeleton of the Nervous System. Advances in Neurobiology, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6787-9_16

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