Neuroimmunomodulatory steroids in Alzheimer dementia.
Though pathobiochemical and neurochemical changes and accompanied morphological alterations in Alzheimer dementia are well known, the triggering mechanisms, if any, remain obscure. Important factors influencing the development and progression of Alzheimer disease include hormonal steroids and their metabolites, some of which may serve as therapeutic agents. This review focusses on major biochemical alterations in the brain of Alzheimer patients with respect to the involvement of steroids. It includes their role in impairment of fuel supply and in brain glycoregulation, with especial emphasis on glucocorticoids and their counter-regulatory steroids as dehydroepiandrosterone and its metabolites. Further, the role of steroids in beta-amyloid pathology is reviewed including alterations in tau-protein(s) phosphorylation. The (auto)immune theory of Alzheimer dementia is briefly outlined, pointing to the possible involvement of steroids in brain ageing, immunosenescence and neuronal apoptosis. Some effects of steroids are briefly mentioned on the formation and removal of reactive oxygen species and their effect on calcium flux and cytotoxicity. The recent biochemical research of Alzheimer disease focusses on molecular signalling at which steroids also take part. New findings may be anticipated when the mosaic describing the molecular mechanisms behind these events becomes more complete.
Institute of Endocrinology, Prague, Czech Republic. rhampl@endo.cz
Richard
R
Hampl
Marie
M
Bicíková
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology* / Q000627:therapeutic use; D006031:Glycosylation; D006801:Humans; D015213:Neuroimmunomodulation / Q000187:drug effects; D013256:Steroids / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005938:Glucocorticoids; D013256:Steroids; D016875:tau Proteins; D003687:Dehydroepiandrosterone