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.
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.
Bajaj
N P
NP
Department of Neurosciences, Institute of Psychiatry, London, UK.
al-Sarraj
S T
ST
Leigh
P N
PN
Anderson
V
V
Miller
C C
CC
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
D017931:DNA Primers; D000939:Epitopes; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases