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12:57
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Prion diseases and emerging prion diseases.
Takashi Yokoyama1, Shirou Mohri
1Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki, Japan. tyoko@affrc.go.jp
Current Medicinal Chemistry
|May 14, 2008
Summary
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders. Emerging atypical TSEs, like Nor98 scrapie and atypical BSE, show distinct prion protein (PrPSc) characteristics, challenging disease classification.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders.
- The abnormal prion protein isoform (PrPSc) is the infectious agent, distinguished from cellular PrP (PrPC) by proteinase K (PK) resistance.
- PrPSc exhibits varying glycoform patterns, reflecting different prion strains.
Purpose of the Study:
- To investigate emerging phenotypes of TSEs with distinct PrPSc characteristics.
- To understand the biochemical basis of these atypical prion diseases, including Nor98 scrapie and atypical bovine spongiform encephalopathy (BSE).
Main Methods:
- Western blot analysis to detect and characterize PrPSc glycoforms.
- Assessment of PrPSc resistance to proteinase K (PK) digestion.
- Classification of atypical BSE into H-type and L-type based on PrPSc molecular weight.
Main Results:
- Atypical TSEs exhibit altered PrPSc glycoform patterns and/or reduced PK resistance compared to typical cases.
- Nor98 represents an atypical scrapie in sheep previously considered resistant.
- Atypical BSE cases (H-type and L-type) show distinct molecular weight profiles.
Conclusions:
- Emerging prion diseases possess unique PrPSc biochemical signatures.
- Conformational variations in PrPSc are likely responsible for the distinct biological and biochemical properties of these novel prion strains.
- Further research is needed to elucidate the origin and full implications of these atypical TSEs.
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