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Molecular Neurobiology

, Volume 38, Issue 1, pp 27–65 | Cite as

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

  • Rodolphe Perrot
  • Raphael Berges
  • Arnaud Bocquet
  • Joel EyerEmail author
Article

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.

Keywords

Neurofilament Intermediate filaments Cytoskeleton Axonal transport Neurodegenerative diseases 

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

Notes

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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Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Rodolphe Perrot
    • 2
  • Raphael Berges
    • 1
  • Arnaud Bocquet
    • 3
  • Joel Eyer
    • 1
    Email author
  1. 1.Laboratoire de Neurobiologie and TransgeneseUPRES-EA3143, INSERM IFR132AngersFrance
  2. 2.Centre de Recherche du Centre Hospitalier Universitaire de QuébecDepartment of Anatomy and Physiology of Laval UniversityQuebecCanada
  3. 3.Division des Maladies Cardiovasculaires IICentre de Recherche Pierre FabreCastresFrance

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