Summary
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 display-polymerase 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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Brene S, Lindefors N, Ehrlich M, Taubes T, Horiuchi A, Kopp J, Hall H, Sedvall G, Greengard P, Persson H (1994) Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue. J Neurosci 14: 985–998
Browning MD, Huganir R, Greengard P (1985) Protein phosphorylation and neuronal function. J Neurochem 45: 11–23
Dierssen M, Vallina IF, Baamonde C, Lumbreras MA, Martinez-Cue C, Calatayud SG, Florez J (1996) Impaired cyclic AMP production in the hippocampus of a Down syndrome murine model. Brain Res Dev Brain Res 95: 122–124
Dierssen M, Vallina IF, Baamonde C, Garcia-Calatayud S, Lumbreras MA, Florez J (1997) Alternations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome. Brain Res 749: 238–244
Frank DA, Greenberg ME (1994) CREB: a mediator of long-term memory from mol- lusks to mammals. Cell 79: 5–8
Frey U, Huang Y-Y, Kandel ER (1993) Effects of cAMP stimulate a late stage of LTP in hippocampal CA1 neurons. Science 260: 1661–1664
Girault J-A, Shalaby IA, Rosen NL, Greengard P (1988) Regulation by cAMP and vasoactive intestinal peptide of phosphorylation of specific proteins in striatal cells in culture. Proc Natl Acad Sci USA 85: 7790–7794
Girault J-A, Horiuchi A, Gustafson EL, Rosen NL, Greengard P (1990) Differential expression of ARPP-16 and ARPP-19, two highly related cAMP-regulated phospho-proteins, one of which is specially associated with dopamine-innervated brain region. J Neurosci 10: 1124–1133
Greengard P (1987) Neuronal phosphoproteins. Mediators of signal transduction. Mol Neurobiol 1: 81–119
Horiuch A, Williams KR, Kurihara T, Nairn AC, Greengard P (1990) Purification and cDNA cloning of ARPP-16, a cAMP-regulated phosphoprotein enriched in basal ganglia, and of a related phosphoprotein, ARPP-19. J Biol Chem 265: 9476–9484
Linden DJ, Ahn S (1999) Activation of presynaptic cAMP-dependent protein kinase is required for induction of cerebellar long-term potentiation. J Neurosci 19: 10221– 10227
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41: 479–486
Nairn AC, Hemmings HC Jr, Greengard P (1985) Protein kinases in the brain. Ann Rev Biochem 54: 931–976
Nestler EJ, Greengard P (1983) Protein phosphorylation in the brain. Nature 305: 583–588
Ohm TG, Bohl J, Lemmer B (1989) Reduced cAMP-signal transduction in postmortem hippocampus of demented old people. Prog Clin Biol Res 317: 501–509
Parks KM, Sugar JE, Haroutunian V, Bierer L, Perl D, Wallace WC (1991) Reduced in vitro phosphorylation of synapsin I (site 1) in Alzheimer’s disease postmortem tissues. Brain Res Mol Brain Res 9: 125–134
Perdahl E, Adolfsson R, Alafuzoff I, Albert KA, Nestler EJ, Greengard P, Winblad B (1984) Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multi-infarct dementia. J Neural Transm 60: 133–141
Ross BM, McLaughin M, Roberts M, Milligan G, McCulloch J, Knowler JT (1993) Alternations in the activity of adenylate cyclase and high affinity GTPase in Alzheimer’s disease. Brain Res 622: 35–42
Schnecko A, Witte K, Bohl J, Ohm T, Lemmer B (1994) Adenylyl cyclase activity in Alzheimer’s disease brain: stimulatory and inhibitory signal transduction pathways are differently affected. Brain Res 644: 291–296
Siarey RJ, Carlson EJ, Epstein CJ, Balbo A, Rapoport SI, Galdzicki Z (1999) Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome. Neuropharmacology 38: 1917–1920
Tierney MC, Fisher RH, Lewis AJ, Zorzitto ML, Snow WG, Reid DW, Nieuwstraten P (1998) The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease: a clinicopathologic study of 57 cases. Neurology 38: 359–364
Walaas SI, Greengard P (1991) Protein phosphorylation and neuronal function.Pharmacol Rev 43: 299–349
Yamamoto M, Ozawa H, Saito T, Frolich L, Riederer P, Takahata N (1996) Reduced immunoreactivity of adenylyl cyclase in dementia of the Alzheimer type.Neuroreport 7: 2965–2970
Yamamoto M, Ozawa H, Saito T, Hatta S, Riederer P, Takahata N (1997) Ca2+/CaM-sensitive adenylyl cyclase activity is decreased in the Alzheimer’s brain: possible relation to type I adenylyl cyclase. J Neural Transm 104: 721–732
Yamamoto-Sasaki M, Ozawa H, Saito T, Rosier M, Riederer P (1999) Impaired phosphorylation of cyclic AMP response element binding protein in the hippocampus of dementia of the Alzheimer type. Brain Res 824: 300–303
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag/Wien
About this chapter
Cite this chapter
Kim, S.H., Nairn, A.C., Cairns, N., Lubec, G. (2001). Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer’s disease. In: Lubec, G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_21
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6262-0_21
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83704-7
Online ISBN: 978-3-7091-6262-0
eBook Packages: Springer Book Archive