Neurofilament Proteins in Brain Diseases

Neurofilaments are the main components of intermediate filaments in neurons, and are expressed under three different subunit proteins, NFL, NFM and NFH. Neurofilaments act with microtubules and microfilaments to form and maintain the neuronal structure and cell shape. Phosphorylation is the main post-translational modification of neurofilaments, which influences their polymerization and depolymerization, and is responsible for their correct assembly, transport, organization and function in the neuronal process. In particular, phosphorylation is essential for the repulsion of the neurofilament polymers in axons, which determines the axonal diameter and the velocity of electrical conduction. The phosphorylation state of neurofilaments is regulated in a complex manner, including interactions with the neighbouring glial cells. Abnormal expression, accumulation or post-translational modifications of neurofilament proteins are found in an increasing number of described neurological diseases, such as amyotrophic lateral sclerosis, Parkinson’s, Alzheimer’s and CharcotMarie-Tooth diseases, or giant axonal neuropathy. Some of these diseases are associated with mutations discovered in the neurofilament genes. Recently, altered expression and phosphorylation states of neurofilament proteins have also been shown in metabolic diseases affecting the central nervous system either during development or in adulthood, such as hepatic encephalopathy due to hyperammonemia, methylmalonic and propionic acidemias, and diabetic neuropathy. Finally, accumulation of neurofilament proteins in ∗ Correspondence to: Olivier Braissant. Clinical Chemistry Laboratory, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland; Tél: (+41.21) 314.41.52; Fax: (+41.21) 314.35.46; e-mail: [email protected] This article may be freely distributed for all and any purposes excluding commercial transactions. While reasonable care has been taken in the preparation of this digital document, the publisher makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising from the information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services. Olivier Braissant 26 the cerebrospinal fluid has been described as discriminating marker for patients with multiple sclerosis, and as predictor of long-term outcome after cardiac arrest. This review will focus on the most recent investigations on neurofilament proteins in neurodegenerative, neurodevelopmental and metabolic diseases, as well as on the use of neurofilaments as markers of diseases.