Pathological immuno-reactions of glial cells in Alzheimer's disease and possible sites of interference.
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 beta-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 strengthens 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.
Schubert
P
P
Department of Neuromorphology, Max Planck Institute for Neurobiology, Martinsried, Federal Republic of Germany.
Ogata
T
T
Miyazaki
H
H
Marchini
C
C
Ferroni
S
S
Rudolphi
K
K
D000241:Adenosine / Q000502:physiology; D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D017628:Microglia / Q000473:pathology / Q000502:physiology; D008959:Models, Neurological; D009457:Neuroglia / Q000276:immunology / Q000473:pathology*; D015290:Second Messenger Systems; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium