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

Prog Neuropsychopharmacol Biol Psychiatry. 1999 Jul;23(5):833-50. doi: 10.1016/s0278-5846(99)00044-5.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / immunology*
  • Animals
  • Blotting, Western
  • COS Cells
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases / metabolism*
  • DNA Primers
  • Epitope Mapping
  • Epitopes / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Motor Neurons / enzymology
  • Motor Neurons / metabolism*
  • Neurofilament Proteins / immunology
  • Neurofilament Proteins / metabolism*
  • Peptide Fragments / chemical synthesis
  • Phosphorylation

Substances

  • DNA Primers
  • Epitopes
  • Neurofilament Proteins
  • Peptide Fragments
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human
  • Cyclin-Dependent Kinases