Immune-inflammatory responses and oxidative stress in Alzheimer's disease: therapeutic implications.
Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and oxidative stress. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Abeta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Inflammation clearly occurs in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e. environmental factors (pro-inflammatory phenotype) and/or genetic factors (pro-inflammatory genotype) have been described. Irrespective of the source and mechanisms that lead to the generation of reactive oxygen species, mammalian cells have developed highly regulated inducible defence systems, whose cytoprotective functions are essential in terms of cell survival. When appropriately activated, each one of these systems has the possibility to restore cellular homeostasis and rebalance redox equilibrium. Increasing evidence, support the notion that reduction of cellular expression and activity of antioxidant proteins and consequent augment of oxidative stress are fundamental causes for ageing processes and neurodegenerative diseases., including AD. The better understanding of different molecular and cellular inflammatory mechanisms is crucial for complete knowledge of AD pathophysiology, hence for its prevention and drug therapy. Accordingly, two lines of preventive therapeutics can be outlined, the first based on anti-inflammatory drugs, the second one on anti-oxidative properties.
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Immunosenescence Unit, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
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Candore
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Castiglia
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Colonna-Romano
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D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology*
D018836:Inflammation Mediators