Neurodegenerative diseases and intermediate filaments

Abstract

Intermediate filaments (IFs) represent the most abundant cytoskeletal constituent in mature neurons. Their mutations and/or accumulations are associated with many human neurodegenerative disorders and it is now well established that disorganization of the intermediate filament network may be directly involved in neurodegeneration. Diseases caused by intermediate filament abnormalities show a wide range of phenotypes, depending on many factors, including the class of affected intermediate filaments and the type of mutation. Various mouse models were extensively used to provide a better understanding of the role played by the disorganization of intermediate filaments in the pathogenesis of neurodegenerative disorders. However, the mechanisms leading to the formation of these aggregates often remain elusive. Multiple factors can potentially induce the accumulation of neuronal intermediate filaments, including dysregulation of intermediate filament gene expression, intermediate filament mutations, defective axonal transport, abnormal posttranslational modifications, and/or proteolysis. Here, we review some neurodegenerative diseases involving intermediate filament abnormalities and possible mechanisms susceptible to provoke them.