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

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Protein Expression in Down Syndrome Brain

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.

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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

    PubMed  CAS  Google Scholar 

  • Browning MD, Huganir R, Greengard P (1985) Protein phosphorylation and neuronal function. J Neurochem 45: 11–23

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Frank DA, Greenberg ME (1994) CREB: a mediator of long-term memory from mol- lusks to mammals. Cell 79: 5–8

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Greengard P (1987) Neuronal phosphoproteins. Mediators of signal transduction. Mol Neurobiol 1: 81–119

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Nairn AC, Hemmings HC Jr, Greengard P (1985) Protein kinases in the brain. Ann Rev Biochem 54: 931–976

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ, Greengard P (1983) Protein phosphorylation in the brain. Nature 305: 583–588

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Walaas SI, Greengard P (1991) Protein phosphorylation and neuronal function.Pharmacol Rev 43: 299–349

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

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© 2001 Springer-Verlag/Wien

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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

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  • 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

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