Cortical neurons of Creutzfeldt-Jakob disease patients express the urokinase-type plasminogen activator receptor.
Plasminogen belongs to the plasminogen activator system of cell signaling proteins and has recently been identified to bind to pathological prion protein PrPSC, but not to its normal conformer, PrPC. Plasminogen binds specifically to the urokinase-type plasminogen activator receptor (uPAR) to promote pericellular proteolysis, regulate integrin function, and mediate cell signaling. By using immunohistochemistry, we observed that significantly more cortical neurons in eight postmortem brains of patients who died with sporadic Creutzfeldt-Jakob disease (CJD) are immunoreactive for uPAR compared with controls. These data provide the pathophysiological basis for detailed analyses of the role of the plasminogen activator system in CJD and related diseases.
Deininger
M H
MH
Institute of Brain Research, University of Tuebingen, Medical School, Calwer Strasse 3, 72076, Germany. martin.deininger@uni-tuebingen.de
Trautmann
K
K
Magdolen
V
V
Luther
T
T
Schluesener
H J
HJ
Meyermann
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D000949:Histocompatibility Antigens Class II; C524898:PLAUR protein, human; D018620:PrPSc Proteins; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D010751:Phosphopyruvate Hydratase