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Review of the Multiple Aspects of Neurofilament Functions, and their Possible Contribution to Neurodegeneration

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Abstract

Neurofilaments (NF) are the most abundant cytoskeletal component of large myelinated axons from adult central and peripheral nervous system. Here, we provide an overview of the complementary approaches, including biochemistry, cell biology and transgenic technology that were used to investigate the assembly, axonal transport and functions of NF in normal and pathological situations. Following their synthesis and assembly in the cell body, NFs are transported along the axon. This process is finely regulated via phosphorylation of the carboxy-terminal part of the two high-molecular-weight subunits of NF. The correct formation of an axonal network of NF is crucial for the establishment and maintenance of axonal calibre and consequently for the optimisation of conduction velocity. The frequent disorganisation of NF network observed in several neuropathologies support their contribution. However, despite the presence of NF mutations found in some patients, the exact relations between these mutations, the abnormal NF organisation and the pathological process remain a challenging field of investigation.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

amyotrophic lateral sclerosis

BPAG1n:

bullous pemphigoid antigen 1 neural isoform

CaMKII:

calcium–calmodulin-dependent protein kinase II

CKI/II:

casein kinase I and II

CMT:

Charcot-Marie-Tooth disease

CNS:

central nervous system

GAN:

giant axonal neuropathy

GSK3:

glycogen synthetase kinase 3

IDPN:

β, β‘-iminodipropionitrile

IF:

intermediate filaments

JNK1/3:

c-Jun N-terminus kinase 1 and 3

KSP:

lysine–serine–proline

MAG:

myelin-associated glycoprotein

MAP:

microtubule-associated protein

MF:

microfilaments

MT:

microtubules

NF:

neurofilaments

NFH:

heavy neurofilament subunit

NFL:

light neurofilament subunit

NFM:

medium-sized neurofilament subunit

NFT:

neurofibrillary tangles

NIFID:

neuronal intermediate filament inclusion disease

O-GlcNAc:

O-linked N-acetyl glucosamine

PD:

Parkinson’s disease

PKA:

protein kinase A

PKC:

protein kinase C

PKN:

protein kinase N

PNS:

peripheral nervous system

PP2A:

phosphatase 2A

SAPK:

stress-activated protein kinase

SC:

slow component

SOD1:

superoxide dismutase 1

STOP:

stable tubule only polypeptide

TBCB:

tubulin folding cofactor B

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Acknowledgements

We thank Drs. J.P. Julien and A.C. Peterson for critical reading of this manuscript and helpful scientific suggestions. This work was supported by grants from the Association Française contre les Myopathies, Institut National sur le Cancer and Association pour la Recherche sur la Sclérose en Plaques to J. Eyer.

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Authors and Affiliations

  1. Laboratoire de Neurobiologie and Transgenese, UPRES-EA3143, INSERM IFR132, Batiment Monteclair, CHU, 49033, Angers, France

    Raphael Berges & Joel Eyer

  2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Department of Anatomy and Physiology of Laval University, Quebec, G1V 4G2, Canada

    Rodolphe Perrot

  3. Division des Maladies Cardiovasculaires II, Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106, Castres, France

    Arnaud Bocquet

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  1. Rodolphe Perrot
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  2. Raphael Berges
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  3. Arnaud Bocquet
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  4. Joel Eyer
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Correspondence to Joel Eyer.

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Perrot, R., Berges, R., Bocquet, A. et al. Review of the Multiple Aspects of Neurofilament Functions, and their Possible Contribution to Neurodegeneration. Mol Neurobiol 38, 27–65 (2008). https://doi.org/10.1007/s12035-008-8033-0

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  • DOI: https://doi.org/10.1007/s12035-008-8033-0

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