Summary
A significant role of a pathological glial cell activation in the pathogenesis of Alzheimer’s disease is supported by the growing evidence that inflammatory proteins, which are produced by reactive astrocytes, promote the transformation of diffuse β-amyloid deposits into the filamentous, neurotoxic form. A number of vicious circles, driven by the release of TNF-a and free oxygen radicals from microglial cells, may cause an upregulated microglial activation and their production of interleukin-1 which triggers, secondarily, the crucial activation of astrocytes. Reactive functional changes of glial cells seem to be controlled by an altered balance of the second messengers Ca2+ and cAMP and can be counterregulated by the endogenous cell modulator adenosine which strenghtens the cAMP-dependent signalling chain. A further reinforcement of the homeostatic adenosine effects on glial cells by pharmaca, such as propentofylline, may add to neuroprotection in Alzheimer’s disease.
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References
Abraham CA, Potter H (1989) Alzheimer’s disease: recent advances in understanding the brain amyloid deposits. Biotechnology 7: 147–153
Araujo DM, Cotman CW (1992) β-amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer’s disease. Brain Res 569: 141–145
Banati R, Schubert P, Rothe G, Gehrmann J, Rudolphi K, Valet G, Kreutzberg GW (1994) Modulation of intracellular reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline. J Cereb Blood Flow Metab 14: 145–149
Bowman BH, Yang F, Buchanan JM, Adrian GS, Martinez AO (1996) Human APOE protein localized in brains of transgenic mice. Neurosci Lett 219: 57–59
Buxbaum JD, Ruefli AA, Parker CA, Cypess AM, Greengard P (1994) Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner. Proc Natl Acad Sci USA 91: 4489–4493
Das S, Potter H (1995) Expression of the Alzheimer amyloid-promoting factor antichymotrypsin is induced in human astrocytes by I1–1. Neuron 14: 447–456
DeLeo J, Tóth L, Schubert P, Rudolphi K, Kreutzberg GW (1987) Ischemia-induced neuronal cell death, calcium accumulation and glial response in the hippocampus of the gerbil and protection by the xanthine derivative HWA 285. J Cereb Blood Flow Metab 7: 745–752
Diemer NH, Seitzberg D, Rosdahl D, Nielsen M, Christensen T, Baichen T, Johansen FF (1994) AMPA receptor and metabotropic glutamate receptor mRNA expression after transient global ischemia in the rat. Pathophysiology 1: 107
Dyrcks T, Dyrcks E, Masters CL, Beyreuther K (1993) Amyloidogenicity of rodent and human β A4 sequences. FEBS Lett 324: 231–236
Ferroni S, Marchini C, Schubert P, Rapisarda C (1995) Two distinct inward rectifying conductances are expressed in cultured rat cortical astrocytes after long term dibutyryl-cyclic-AMP treatment. FEBS Lett 267: 319–325
Forloni G, Demicheli F, Giorgi S, Bendotti C, Angeretti N (1992) Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. Mol Brain Res 16: 128–134
Giulian D (1987) Amoeboid microglia as effector of inflammation in the central nervous system. J Neurosci Res 18: 155–171
Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. TINS 19: 312–318
Ma J, Yee A, Brewer HB, Das S, Potter H (1994) Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of beta-protein into filaments. Nature 372: 92–94
McGeer PL, Kawamata T, Walker D, Abyama H, Toyama I, McGeer EG (1993) Microglia in degenerative neurological disease. Glia 7: 84–92
McRae A, Rudolphi K, Schubert P (1994) Propentofylline depresses amyloid and Alzheimer’s CSF microglial antigens after ischemia. NeuroReport 5: 1193–1196
McRae A, Schubert P, Ogata T, Nakamura Y, Ling EA, Kaur C, Rudolphi K (1997) Postischemic glial responses and amyloid accumulation are modified by propentofylline: a neuroprotective pharmacon for Alzheimer’s disease? In: Iqbal K, Winblad B, Nishimura T, Takeda M, Wisniewski HM (eds) Biology, diagnosis and therapeutics. Wiley, New Jersey, pp 759–767
Meda L, Cassatella MA, Szendrei I (1995) Activation of microglial cells by β-amyloid protein and interferon-γ. Nature 374: 647–650
Meskini N, Némoz G, Okyayuz-Baklouti I, Lagard M, Prigent AF (1994) Phosphodiesterase inhibitory profile of some related xanthine derivatives pharmacologically active on the peripheral microcirculation. Biochem Pharmacol 47: 781–788
O’Neill C, Fowler CJ, Winblad B, Cowburn RF (1994) G-protein coupled signal transduction systems in the Alzheimer’s disease brain. Biochem Soc Transact 22:167–171
Ogata T, Nakamura Y, Schubert P (1996) Potentiated cAMP rise in metabotropically stimulated rat cultured astrocytes by a Ca2+-related A1/A2 adenosine receptor cooperation. Eur J Neurosci 8: 1124–1131
Parkinson FE, Fredholm BB (1991) Effects of propentofylline on adenosine A1 and A1 receptors and nitrobenzylthioinosine-sensitive neucleoside transporters: quantitative autoradiographic analysis. Eur J Pharmacol 202: 361–366
Schubert P, Rudolphi K, Fredholm F, Nakamura Y (1994) Modulation of nerve and glial cell function by adenosine — role in the development of ischemic brain damage. Int J Biochem 26: 1227–1236
Schubert P, Ogata T, Rudolphi K (1997) Depression of TNF-a release from microglial cells by adenosine and propentofylline. J Cereb Blood Flow Cell Metab 17 [Suppl 1]: S718
Schubert P, Ogata T, Rudolphi K, Marchini C, McRae A, Ferroni S (1997) Support of homeostatic glial cell signalling: a novel therapeutic approach by propentofylline. In: de la Torre JC, Hachinski V (eds) Cerebrovascular pathology in Alzheimer’s disease. Ann NY Acad Sci 826: 337–347
Sheng JG, Mrak RE, Griffin WS (1996) Apolipoprotein E distribution among different plaque types in Alzheimer’s disease: implications for its role in plaque progression. Neuropathol Appl Neurobiol 22: 334–341
Si Q, Nakamura Y, Schubert P, Rudolphi K, Kataoka K (1996) Adenosine and propentofylline inhibit phorbol ester-induced proliferation of cultured microglia. Exp Neurol 137: 345–349
Wekerle H, Linington C, Lassmann H, Meyermann R (1986) Cellular immune reactivity within the CNS. TINS 9: 271–277
Wisniewsky T, Frangione B (1992) Apolipoprotein E: a pathological chaperone in patients with cerebral amd systemic amyloid. Neurosci Lett 135: 235–238
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Schubert, P., Ogata, T., Miyazaki, H., Marchini, C., Ferroni, S., Rudolphi, K. (1998). Pathological immuno-reactions of glial cells in Alzheimer’s disease and possible sites of interference. In: Gertz, HJ., Arendt, T. (eds) Alzheimer’s Disease — From Basic Research to Clinical Applications. Journal of Neural Transmission. Supplementa, vol 54. Springer, Vienna. https://doi.org/10.1007/978-3-7091-7508-8_16
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DOI: https://doi.org/10.1007/978-3-7091-7508-8_16
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83112-0
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