Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer's disease.

Abstract

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.

• Authors: S H Kim, A C Nairn, N Cairns, G Lubec
• Journal: Journal of neural transmission. Supplementum (J Neural Transm Suppl) Issue 61 Pg. 263-72 ( 2001) ISSN: 0303-6995 [Print] Austria
• PMID: 11771749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphoproteins
• RNA, Messenger
• cyclic AMP-regulated phosphoprotein 19
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases

Topics

• Alzheimer Disease (metabolism, physiopathology)
• Base Sequence
• Brain (metabolism)
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Down Syndrome (metabolism, physiopathology)
• Gene Expression Profiling
• Humans
• Molecular Sequence Data
• Phosphoproteins (genetics, metabolism)
• Phosphorylation
• RNA, Messenger (metabolism)
• Signal Transduction