Modifications of microtubule proteins in ALS nerve precede detectable histologic and ultrastructural changes

Fast axonal transport is altered in nerves from amyotrophic lateral sclerosis (ALS) patients. Microtubules are involved in axonal transport. We analyzed the possibility of an involvement of microtubule modifications underlying the alterations in transport using biochemical and morphologic analysis of intercostal nerves from ALS and control patients. In intercostal nerves displaying no morphologic signs of acute neuronal degeneration, two-dimensional gels showed modifications of the group of β tubulins and abnormal spots of proteins, some appearing to be closely related to tau proteins. These results suggest that microtubule proteins are modified in ALS before ultrastructural axonal degeneration, but the significance of these abnormalities remains hypothetical.

[1]  V. Meininger,et al.  Biochemical basis of microtubule cold stability in the peripheral and central nervous systems , 1988, Brain Research.

[2]  V. Meininger,et al.  Heterogeneity of cold-stable and cold-labile tubulin in axon- and soma-enriched portions of the adult mouse brain , 1987, Neuroscience Letters.

[3]  S. M. Chou,et al.  Fast axonal transport in amyotrophic lateral sclerosis , 1987, Neurology.

[4]  L. Binder,et al.  Biochemical and immunological analyses of cytoskeletal domains of neurons , 1986, The Journal of cell biology.

[5]  W. Bradley,et al.  Amyotrophic leteral sclerosis: Part 2. Etiopathogenesis , 1985 .

[6]  W. Bradley,et al.  Amyotrophc Lateral Sclerosis: Part 1. Clinical Features, Pathology, and E h c d Issues in Management* , 2004 .

[7]  D. Weiss,et al.  Gliding movement of and bidirectional transport along single native microtubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport , 1985, The Journal of cell biology.

[8]  R. Lasek,et al.  Axonal tubulin and axonal microtubules: biochemical evidence for cold stability , 1984, Journal of Cell Biology.

[9]  W. Bradley,et al.  Morphometric and biochemical studies of peripheral nerves in amyotrophic lateral sclerosis , 1983, Annals of neurology.

[10]  I. Gozes Tubulin in the nervous system , 1982, Neurochemistry International.

[11]  P. Denoulet,et al.  High level of tubulin microheterogeneity in the mouse brain , 1982, Neuroscience Letters.

[12]  R. Vallee A taxol-dependent procedure for the isolation of microtubules and microtubule-associated proteins (MAPs) , 1982, The Journal of cell biology.

[13]  J. Lee,et al.  Polymorphism of brain tubulin. , 1981, Biochemistry.

[14]  M. Kirschner,et al.  Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. , 1977, Journal of molecular biology.

[15]  P. O’Farrell High resolution two-dimensional electrophoresis of proteins. , 1975, The Journal of biological chemistry.

[16]  S. Carpenter Proximal axonal enlargement in motor neuron disease , 1968, Neurology.

[17]  J. Šťastný,et al.  Determination of relative amounts of silver stained proteins on two‐dimensional gels using internal calibrator , 1986 .

[18]  R. Dernick,et al.  Simplified method for silver staining of proteins in polyacrylamide gels and the mechanism of silver staining , 1985 .

[19]  A. Hirano Aspects of the ultrastructure of amyotrophic lateral sclerosis. , 1982, Advances in neurology.

[20]  N. Morris,et al.  Identification of a gene for beta-tubulin in Aspergillus nidulans. , 1978, Cell.