Abstract
1. Accumulations of phosphorylated neurofilaments are seen in affected motor neurones in amyotrophic lateral sclerosis (ALS). 2. The authors demonstrate that cyclin dependent kinase-5 (cdk-5) will induce cellular phosphorylation of neurofilament heavy chain side-arms to generate epitopes for several antibodies that label these neurofilament accumulations. 3. By creating recombinant neurofilament fragments of NF-H side-arm domains, the authors also map the epitopes for several of these antibodies. 4. Finally, the authors demonstrate that cdk-5 is also present in affected motor neurones in ALS. These studies implicate cdk-5 in the pathogenesis of ALS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Amino Acid Sequence
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Amyotrophic Lateral Sclerosis / enzymology
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Amyotrophic Lateral Sclerosis / immunology*
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Animals
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Blotting, Western
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COS Cells
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / metabolism*
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DNA Primers
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Epitope Mapping
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Epitopes / biosynthesis*
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Female
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Humans
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Immunohistochemistry
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Male
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Middle Aged
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Molecular Sequence Data
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Motor Neurons / enzymology
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Motor Neurons / metabolism*
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Neurofilament Proteins / immunology
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Neurofilament Proteins / metabolism*
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Peptide Fragments / chemical synthesis
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Phosphorylation
Substances
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DNA Primers
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Epitopes
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Neurofilament Proteins
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Peptide Fragments
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Cyclin-Dependent Kinase 5
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CDK5 protein, human
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Cyclin-Dependent Kinases