title: Cyclin dependent kinase-5 (CDK-5) phosphorylates neurofilament heavy (NF-H) chain to generate epitopes for antibodies that label neurofilament accumulations in amyotrophic lateral sclerosis (ALS) and is present in affected motor neurones in ALS.
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.
authors.affiliation: Department of Neurosciences, Institute of Psychiatry, London, UK.
authors.forename: N P
authors.initials: NP
authors.lastname: Bajaj
authors.forename: S T
authors.initials: ST
authors.lastname: al-Sarraj
authors.forename: P N
authors.initials: PN
authors.lastname: Leigh
authors.forename: V
authors.initials: V
authors.lastname: Anderson
authors.forename: C C
authors.initials: CC
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D017931:DNA Primers; D018604:Epitope Mapping; D000939:Epitopes / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000201:enzymology / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis; D010766:Phosphorylation
chemical_list: D017931:DNA Primers; D000939:Epitopes; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases