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.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Autophagy / drug effects
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Central Nervous System / drug effects
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Central Nervous System / metabolism
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Central Nervous System / pathology*
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Gene Expression Regulation
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Humans
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NAD / pharmacology
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology*
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Prion Diseases / drug therapy
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Prion Diseases / genetics
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Prion Diseases / metabolism
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Prion Diseases / pathology*
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Prions / drug effects
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Prions / genetics
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Prions / metabolism
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Prions / pathogenicity*
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Protein Folding
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Ubiquitin / genetics
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Ubiquitin / metabolism
Substances
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Apoptosis Regulatory Proteins
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Prions
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Transcription Factors
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Ubiquitin
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NAD