title: Amyloid, amyloid-inducers, cytokines and heavy metals in scrapie and other human and animal subacute spongiform encephalopathies: some hypotheses.
abstract: A number of hypotheses regarding the pathogenesis of scrapie and other human and animal spontaneous and experimental subacute spongiform encephalopathies (SSE) are presented here. In particular, it is speculated that a PrPsc 27-30-induced suppression of host's defense system is responsible, through the existence of the different and synergistically operating mechanisms, for the absence of any documented inflammatory or immunologic response during SSE. This could be therapeutically counterparted by the utilization of cytokines (TNF, IL-1, etc) or cytokine-inducers, provided that synthesis and secretion of the above inflammation mediators on behalf of reticulo-endothelial cells were strongly depressed by PrP 27-30, as suggested. Finally, some hypotheses are also made in relation to the blood-brain-barrier's integrity in susceptible hosts. Similarly to Alzheimer's disease (AD) in man, this could play a role also in SSE pathogenesis, facilitating cerebral localization of metals such as aluminum, lead, or silica, which have already been shown to enhance amyloid fibrils' polymerization and deposition within human brain tissue.
authors.affiliation: Istituto Superiore di Sanità, Laboratorio di Medicina Veterinaria, Rome, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Agrimi
authors.forename: G
authors.initials: G
authors.lastname: Di Guardo
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000682:Amyloid / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology*; D004351:Drug Resistance / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008670:Metals / Q000378:metabolism* / Q000633:toxicity; D008954:Models, Biological; D017096:Prion Diseases / Q000503:physiopathology*; D012608:Scrapie / Q000503:physiopathology*
chemical_list: D000682:Amyloid; D016207:Cytokines; D006023:Glycoproteins; D008670:Metals