Intermediate filaments in peripheral nervous system: Their expression, dysfunction and diseases

Characteristics of the intermediate filament proteins (IFPs) expressed during the development and cell differentiation of peripheral neurons are here reviewed. Neurofilament triplet proteins (NFPs), peripherin, α-internexin, synemin, syncoilin, nestin, vimentin and glial fibrillary acidic protein (GFAP) are each produced by different genes. NFPs, the most extensively studied, are thought to maintain axonal caliber, thus ensuring normal axonal transport, but this network is highly disrupted in several diseases, particularly motor neuron diseases. α-internexin has been proposed as the fourth NFP subunit. The relative plasticity of the peripherin network may account for its possible role during development, when axons have to find their targets, and when axons regenerate. In addition to their expression in muscle, other IFPs, such as syncoilin and synemin, are also expressed in neuronal tissues. Syncoilin modulates peripherin filament networks. Synemin M, associated with peripherin, is present in small unmyelinated fibers, whereas synemin L is produced in large neurons with myelinated fibers positive for the light-chain neurofilament (NF-L) subunit. Nestin is an IFP expressed in dividing cells during early stages of development in the central and peripheral nervous systems, and in muscles and other tissues. After differentiation, nestin is downregulated and replaced by tissue-specific IFPs. IFPs in glial cells are primarily composed of GFAP, although vimentin is also expressed; vimentin is also widely distributed in mesenchymal derivatives and established cell lines. In the peripheral nervous system, NFPs appear early in its development and progressively replace vimentin, which is expressed before NFPs in most, if not all, dividing neuroepithelial cells. In addition, in tissues undergoing an injury response, the unique and complex cell and tissue distribution of IFPs can be markedly modified.