title: Mechanisms of prion-induced neurodegeneration.
abstract: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrP(C)), termed PrP(TSE), are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes. Accordingly, several mechanisms of prion-mediated neurotoxicity have been proposed. In this paper, we provide an overview of the recent knowledge on the mechanisms of neuropathogenesis, the neurotoxic PrP species and the possible therapeutic approaches to treat these devastating disorders.
authors.affiliation: Scientific Affairs,Holland Laboratory,American Red Cross,Rockville, MD,USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Saá
authors.affiliation: Department of Biochemistry,Boston University School of Medicine,Boston, MA,USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Harris
authors.affiliation: Scientific Affairs,Holland Laboratory,American Red Cross,Rockville, MD,USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Cervenakova
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D009243:NAD / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017096:Prion Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011328:Prions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017510:Protein Folding; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D011328:Prions; D014157:Transcription Factors; D025801:Ubiquitin; D009243:NAD