title: Transmission of prions within the gut and towards the central nervous system.
abstract: The prion protein is a glycoprotein characterized by a folded α-helical structure that, under pathological conditions, misfolds and aggregates into its infectious isoform as β-sheet rich amyloidic deposits. The accumulation of the abnormal protein is responsible for a group of progressive and fatal disorders characterized by vacuolation, gliosis, and spongiform degeneration. Prion disorders are characterized by a triple aetiology: familial, sporadic or acquired, although most cases are sporadic. The mechanisms underlying prion neurotoxicity remain controversial, while novel findings lead to hypothesize intriguing pathways responsible for prion spreading. The present review aims to examine the involvement of the gastrointestinal tract and hypothesizes the potential mechanisms underlying cell-to-cell transmission of the prion protein. In particular, a special emphasis is posed on the mechanisms of prion transmission within the gut and towards the central nervous system. The glycation of prion protein to form advanced glycation end-products (AGE) interacting with specific receptors placed on neighboring cells (RAGE) represents the key hypothesis to be discussed.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Natale
authors.forename: Michela
authors.initials: M
authors.lastname: Ferrucci
authors.forename: Gloria
authors.initials: G
authors.lastname: Lazzeri
authors.forename: Antonio
authors.initials: A
authors.lastname: Paparelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D011328:Prions / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D011328:Prions; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic