Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer's disease.
ARPP-19 (cAMP-regulated phosphoprotein of Mr = 19,000) is a substrate for cAMP-dependent protein kinase (PKA). ARPP-19 is found in all brain regions but the function of ARPP-19 is not fully elucidated yet. We detected a downregulated sequence with 100% homology with ARPP-19 in temporal cortex of patients with Down syndrome (DS) as compared to controls, but not in Alzheimer's disease (AD) using differential displaypolymerase chain reaction (DD-PCR). We subsequently determined protein levels of ARPP-19 in temporal cortex and cerebellum by immunoblotting and observed significant reduction of ARPP-19 in DS (temporal cortex) and AD (cerebellum). We also observed decreased activities of PKA in DS (temporal cortex and cerebellum) and AD (temporal cortex). These findings suggest that decreased ARPP-19 along with decreased activities of PKA is involved in pathomechanisms of both neurodegenerative disorders. Furthermore, these findings provide first evidence for an impaired mechanism of cAMP-related signal transduction and phosphorylation in both dementing disorders.
Kim
S H
SH
Department of Pediatrics, University of Vienna, Austria.
Nairn
A C
AC
Cairns
N
N
Lubec
G
G
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004314:Down Syndrome / Q000378:metabolism* / Q000503:physiopathology; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
D010750:Phosphoproteins; D012333:RNA, Messenger; C064321:cyclic AMP-regulated phosphoprotein 19; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases