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Printable Handouts
Navigable Slide Index
- Introduction
- Degenerative diseases of the CNS
- Human prion diseases
- Bioassays in hamsters and discovery of PrP
- Structures of prion protein isoforms
- PrP gene mutations cause inherited prion diseases
- PrP - crystal of 28d / SHaPrP 29-232
- X-ray studies of PrP - 28d antibody fragments
- NMR and X-ray structures of PrP
- Prion protein gene structure and protein products
- Two dimensional crystals of PrP 27-31
- Image reconstruction results
- Beta-helices exist as trimers
- Refined PrPSc model overlaid onto crystal lattice
- Building an amyloid fiber
- Tertiary structures of PrPC and PrPSc
- Some features of prion formation
- Energetics of PrPC conversion into PrPSc
- Synthetic prions
- A transgenic host sensitive to prion infection
- Inoculation of beta-rich isoforms of MoPrP(89-143)
- Making amyloid is a correlate of infectivity
- Analysis of MoPrP(89-230)
- Polymerization of recMoPrP(89-230)
- Matching the mouse to the inoculum
- Tg9949 mice develop prion disease
- Protease resistant PrP in inoculated Tg9949
- Neurohistology of pons of Tg9949 mice
- Astrocytic gliosis in inoculated Tg9949 mice
- Serial transmission of synthetic SMP1 prions
- Second passage of synthetic prions in Tg9950
- Serial passage of synthetic prions to other mice
- Protease K resistant PrP from SMP1 prions
- Pons of Tg9949 passaged in wt FVB mice
- Synthetic mammalian prions
- Heterocyclic pharmacotherapies for prion disease
- Proposed PrPSc replication cycle
- Pyridinyl-based therapies
- Compound-60 analogues
- Pyridinyl-based therapies - Q168
- Pyridinyl-based therapies - new leads
- Pyridinyl-based therapies - T215
- Pyridinyl-based therapies - thienopyridines
- Acridine-based therapies
- Acridine and phenothiazine-based therapies
- Acridine-based therapies - quinacrine
- Treatment with quinacrine cures ScN2a cells
- Could acridine dimers be more potent?
- Cellular efficacy correlates with linker length
- Efficacy and cytotoxicity are influenced by linker
- Bis-acridine is ten-fold more potent than quinacrine
- Bis-acridine and PrP co-localize
- Survival of sCJD patients treated with quinacrine
- Treatment of mice inoculated with RML prions
- Concepts from the discovery of prions
- Age-dependent human neurodegenerative diseases
- ND diseases are autosomal dominant
Topics Covered
- Understanding the biophysical aspects of a disease of protein misfolding
- Structural studies of PrPc and PrPsc
- The development of synthetic mammalian prions and the proof of their infectivity and serial transmissibility
- Heterocyclic pharmacotherapies for prion disease
- Pyridinyl based therapies and structure based design
- Serendipitous discovery of acridines as anti-prion agents
- Bisacridines as potent inhibitors of prion replication in cell culture
- The relationship between the prion diseases and other diseases of protein misfolding
Links
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Talk Citation
Cohen, F. (2007, October 1). Prion diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/CYWF3727.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Fred Cohen has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.