Loading presentation...

Present Remotely

Send the link below via email or IM

Copy

Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.

DeleteCancel

Make your likes visible on Facebook?

Connect your Facebook account to Prezi and let your likes appear on your timeline.
You can change this under Settings & Account at any time.

No, thanks

Human prion diseases

No description
by

Justin Komito

on 10 April 2013

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of Human prion diseases

Prions Stanley Prusiner coined the term "prion" in 1982 Proteinaceous infectious agent
Have no nucleic acid component
Coded for by the PRNP gene
Cause Transmissible Spongiform Encephalopathies in both humans and animals
All TSEs result in the gradual and irreversible degeneration of the brain and are fatal Basics Proteins Prion Diseases Mabbott et al. Nature Reviews Microbiology advance online publication;
published online 06 February 2006 | doi:10.1038/nrmicro1346 Structure The Human Prion Protein Structure PrP (normal cellular prion protien) is expressed primarily in the neurons and glial cells of the CNS c 253 amino acid sequence consisting of and N-terminal domain, a globular domain, C-terminal domain, and a glycosyl-phosphatidylinositol anchor

Monomeric The globular domain consists of 3 alpha helices and 2 beta sheets Antiapoptotic activity Inhibits Bax, TNF-a, and Dpl-mediated apoptotic pathways in
yeast, mouse, and human cell cultures
Oxidative stress protection KO mice are more susceptible to hydrogen peroxide,
xanthine oxidase, and copper ion induced damage than WT
Transmembrane signaling Typical function of lipid raft localized GPI-anchored proteins

Synaptic structure/function/ PrP is concentrated in axons and presynaptic clefts; treat-
maintenance ment of hippocampal neurons induces elaboration of axons
and dendrites and increases # of synaptic contacts
Cell adhesion Binding interactions with cell adhesion molecules such as
laminin and neural cell adhesion molecule (N-CAM)
* Copper binding/transport PrP has 4 high- affinity copper binding domains. Cu Binding
causes a conformational change in PrP and endocytosis PrP is expressed primarily in the CNS and also in peripheral tissues and leukocytes Function Aguzzi A, Heikenwalder M. 2006. Pathogenesis of prion diseases: current status andfuture outlook. Nat. Rev. Microbiol. 4:765–75 c Soto, C. 2006. Diagnosing prion diseases: needs, challenges, and hopes. Nature Rev. Micribiol. 2: 809-819. Primary function is unknown; KO mice do not show any developmental or physiological abnormalities PrP sc sc c Structure Same amino acid sequence as PrP Differs at secondary structure level Primarily beta-pleated sheets Promotes oligomerization and amyloid plaque formation Conversion of PrP to PrP c sc Resistant to heat, UV, PK degredation Ko mice injected w/PrP do not develope TSE Occurs intracellularly within endosomes and ER lumen Nucleated polymerization v. Template assistance PRNP Mutations
and prion strains More than 50 mutations in the PRNP gene
have been identified Each mutation corresponds
to a different prion strain
and its associated disease Horwich A.L. & Weissman J.S.; 1997. Deadly conformations – Protein misfoldingin prion disease. Cell; 89:499–510. Van der Kamp, M.W. & Daggett, V.; 2009. The consequences of pathogenic mutations to the human prion protein. Protein engineering , design, and selection; 22(8): 461-468. Hill, A.F., Butterworth, R.J., Joiner, S. et al. 1999. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189 Human Prion Diseases Acquisition Disease Characteristics fCJD
iCJD
sCJD

vCJD

FFI

GSS

Kuru Characterized by SE and amyloid plaque formation in the cerebrum and thlamus. Disease course is less than 2 years from the onset of symptoms. Causes dimentia and myoclonus (muscle twitch). Characterized by SE and amyloid plaque formation in the cerebellum and thlamus. Disease course is months to years from the onset of symptoms. Causes distal pain and psychiatric symptoms. Characterized by SE and amyloid plaque formation in the cerebrum and thlamus. Disease course is 15 months from the onset of symptoms. Causes insomnia, dysautonomia, and motor dysfunction. Characterized by SE and amyloid plaque formation in the cerebellum and brain stem. Disease course is 5-6 years from the onset of symptoms. Causes dimentia and ataxia. Characterized by SE and amyloid plaque formation in the cerebellum. Disease course is 5-6 years from the onset of symptoms. Causes dimentia and ataxia. Summary
Full transcript