Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain

Brain Res. 2004 Jun 4;1010(1-2):69-80. doi: 10.1016/j.brainres.2004.03.008.


The minibrain kinase (Mnb/Dyrk1A) gene is localized in the Down syndrome (DS) critical region of chromosome 21. This gene encodes a proline-directed serine/threonine protein kinase (minibrain kinase-Mnb/Dyrk1A), which is required for the proliferation of distinct neuronal cell types during postembryonic neurogenesis. To study the distribution of Mnb/Dyrk1A during human brain development and aging, we raised Mnb/Dyrk1A-specific antibody (mAb 7F3) and examined 22 brains of normal subjects from 8 months to 90 years of age. We found that neurons were the only cells showing the presence of 7F3-positive product in both cell nucleus and cytoplasm. Nuclear localization supports the concept that Mnb/Dyrk1A may be involved in control of gene expression. Synaptic localization of Mnb/Dyrk1A also supports our previous studies suggesting that Mnb/Dyrk1A is a regulator of assembly of endocytic apparatus and appears to be involved in synaptic vesicle recycling and synaptic signal transmission. Accumulation of numerous 7F3-positive corpora amylacea in the memory and motor system subdivisions in subjects older than 33 years of age indicates that Mnb/Dyrk1A is colocalized with markers of astrocyte and neuron degeneration. Differences in the topography and the amount of Mnb/Dyrk1A in neurons, astrocytes, and ependymal and endothelial cells appear to reflect cell type- and brain structure-specific patterns in trafficking and utilization of Mnb/Dyrk1A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Antibodies
  • Astrocytes / cytology
  • Astrocytes / enzymology
  • Biomarkers
  • Brain / cytology
  • Brain / enzymology*
  • Brain / growth & development*
  • Cell Nucleus / enzymology
  • Cytoplasm / enzymology
  • Dyrk Kinases
  • Endocytosis / physiology
  • Endothelial Cells / enzymology
  • Ependyma / enzymology
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / physiopathology
  • Neurons / cytology
  • Neurons / enzymology*
  • Presynaptic Terminals / enzymology
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases
  • Synaptic Transmission / physiology


  • Antibodies
  • Biomarkers
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases