Publication Type | Academic Article |
Authors | Wegiel J, Kuchna I, Nowicki K, Frackowiak J, Dowjat K, Silverman W, Reisberg B, DeLeon M, Wisniewski T, Adayev T, Chen-Hwang M, Hwang Y |
Journal | Brain Res |
Volume | 1010 |
Issue | 1-2 |
Pagination | 69-80 |
Date Published | 06/04/2004 |
ISSN | 0006-8993 |
Keywords | Brain, Neurons, Protein Serine-Threonine Kinases |
Abstract | 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. |
DOI | 10.1016/j.brainres.2004.03.008 |
PubMed ID | 15126119 |