Activated c-Jun is present in neurofibrillary tangles in Alzheimer's disease brains.
Alzheimer's disease (AD) pathology is characterized by the presence of insoluble beta-amyoid deposits and neurofibrillary tangles containing hyperphosphorylated tau. Increased expression of the immediate early gene product c-Jun has also been reported in post-mortem AD brains, and the presence of upstream regulators of c-Jun has been described in tangle formations. Here, we report the presence of c-Jun specifically phosphorylated on ser-63, but not ser-73, in tangle-bearing neurons and in 'late-stage' extracellular tangles in AD brains. Western blot analysis confirmed the presence of c-Jun phosphorylated on ser-63 but not on ser-73 in AD brain tissue. The expression of differentially phosphorylated c-Jun in the AD brain may reflect the contradictory roles of these phosphorylation sites in neurons. Furthermore, the inappropriate sequestration of phosphorylated c-Jun in tangles in AD brains may contribute to AD pathology and neurodegeneration.
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
A G
AG
Pearson
U T E
UT
Byrne
G A
GA
MacGibbon
R L M
RL
Faull
M
M
Dragunow
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D001921:Brain / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000201:enzymology*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism
D012694:Serine; D048031:JNK Mitogen-Activated Protein Kinases