• Introduction to Protein Folding and Misfolding
• 69 min
  1. Protein folding and misfolding: from theory to therapy

  • Prof. Christopher Dobson
• Stability and Kinetics of Protein Folding
• 55 min
  2. Mechanisms of protein folding reactions

  • Prof. Thomas Kiefhaber
• Protein Folding Theory
• 53 min
  3. Mapping disordered proteins with single-molecule FRET

  • Dr. Hagen Hofmann
• Protein Folding Simulations
• 36 min
  4. Protein folding

  • Prof. Eugene Shakhnovich
• 42 min
  5. Simulating protein folding with full atomistic detail

  • Prof. Vijay Pande
• 58 min
  6. Molecular dynamics simulations of protein dynamics, unfolding and misfolding

  • Prof. Valerie Daggett
• Protein Folding Inside the Cell: Chaperones
• 42 min
  7. Protein folding Inside the cell: macromolecular crowding and protein aggregation

  • Prof. Emeritus R. John Ellis
• 34 min
  8. Chaperone mechanisms in cellular protein folding

  • Prof. Dr. F. Ulrich Hartl
• 60 min
  9. Quality control of proteins mislocalized to the cytosol

  • Dr. Ramanujan Hegde
• Protein Misfolding and Disease
• 44 min
  10. Protein aggregation, metals and oxidative stress in neurodegenerative diseases

  • Prof. David Allsop
• Protein Design
• 33 min
  11. Designing proteins with life sustaining activities 1

  • Prof. Michael Hecht
• 24 min
  12. Designing proteins with life sustaining activities 2

  • Prof. Michael Hecht
• 48 min
  13. Folding and design of helical repeat proteins

  • Prof. Lynne Regan
• 44 min
  14. Design and engineering of zinc-finger domains

  • Prof. Jacqui Matthews
• 47 min
  15. Prediction and design of protein structures and interactions

  • Prof. David Baker
• Amyloid Fibrils: Structure, Formation and Nanotechnology
• 39 min
  16. Amyloid fibrils as functional nanomaterials

  • Prof. Juliet Gerrard
• 37 min
  17. Functional amyloid fibrils from fungi and viruses

  • Prof. Margaret Sunde
• Intrinsically disordered Proteins
• 40 min
  18. Fuzzy protein theory for disordered proteins

  • Prof. Monika Fuxreiter
• Intersection of RNA, translation and protein aggregation.
• 47 min
  19. Expanding roles of RNA-binding proteins in neurodegenerative diseases

  • Prof. Aaron D. Gitler
• Proteostasis
• 49 min
  20. Adapting proteostasis to ameliorate aggregation-associated amyloid diseases

  • Dr. Jeffery W. Kelly
• Archived Lectures *These may not cover the latest advances in the field
• 60 min
  21. Amyloidosis: disease caused by amyloid

  • Prof. Mark Pepys
• 34 min
  22. Protein folding and dynamics from single molecule spectroscopy

  • Prof. Dr. Benjamin Schuler
• 41 min
  23. Prion diseases

  • Prof. Fred Cohen
• 31 min
  24. Basic studies of protein folding and stability: the folding of related protein families

  • Dr. Jane Clarke
• 38 min
  25. Titin I27: a protein with a complex folding landscape

  • Dr. Jane Clarke
• 49 min
  26. Novel proteins from designed combinatorial libraries

  • Prof. Michael Hecht
• 47 min
  27. Fast folding dynamics of small proteins: placing limits on diffusional limits

  • Dr. Stephen Hagen
• 35 min
  28. The sequence determinants of amyloid fibril formation

  • Prof. Fabrizio Chiti

Printable Handouts

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Navigable Slide Index

1. Introduction
2. Degenerative diseases of the CNS
3. Human prion diseases
4. Bioassays in hamsters and discovery of PrP
5. Structures of prion protein isoforms
6. PrP gene mutations cause inherited prion diseases
7. PrP - crystal of 28d / SHaPrP 29-232
8. X-ray studies of PrP - 28d antibody fragments
9. NMR and X-ray structures of PrP
10. Prion protein gene structure and protein products
11. Two dimensional crystals of PrP 27-31
12. Image reconstruction results
13. Beta-helices exist as trimers
14. Refined PrPSc model overlaid onto crystal lattice
15. Building an amyloid fiber
16. Tertiary structures of PrPC and PrPSc
17. Some features of prion formation
18. Energetics of PrPC conversion into PrPSc
19. Synthetic prions
20. A transgenic host sensitive to prion infection
21. Inoculation of beta-rich isoforms of MoPrP(89-143)
22. Making amyloid is a correlate of infectivity
23. Analysis of MoPrP(89-230)
24. Polymerization of recMoPrP(89-230)
25. Matching the mouse to the inoculum
26. Tg9949 mice develop prion disease
27. Protease resistant PrP in inoculated Tg9949
28. Neurohistology of pons of Tg9949 mice
29. Astrocytic gliosis in inoculated Tg9949 mice
30. Serial transmission of synthetic SMP1 prions
31. Second passage of synthetic prions in Tg9950
32. Serial passage of synthetic prions to other mice
33. Protease K resistant PrP from SMP1 prions
34. Pons of Tg9949 passaged in wt FVB mice
35. Synthetic mammalian prions
36. Heterocyclic pharmacotherapies for prion disease
37. Proposed PrPSc replication cycle
38. Pyridinyl-based therapies
39. Compound-60 analogues
40. Pyridinyl-based therapies - Q168
41. Pyridinyl-based therapies - new leads
42. Pyridinyl-based therapies - T215
43. Pyridinyl-based therapies - thienopyridines
44. Acridine-based therapies
45. Acridine and phenothiazine-based therapies
46. Acridine-based therapies - quinacrine
47. Treatment with quinacrine cures ScN2a cells
48. Could acridine dimers be more potent?
49. Cellular efficacy correlates with linker length
50. Efficacy and cytotoxicity are influenced by linker
51. Bis-acridine is ten-fold more potent than quinacrine
52. Bis-acridine and PrP co-localize
53. Survival of sCJD patients treated with quinacrine
54. Treatment of mice inoculated with RML prions
55. Concepts from the discovery of prions
56. Age-dependent human neurodegenerative diseases
57. 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

Series:

• Protein Folding, Aggregation and Design

Categories:

• Biochemistry
• Clinical Practice
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on October 1, 2007
• Archived on April 17, 2016

Financial Disclosures

• Prof. Fred Cohen has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.