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. . Mind Map (Course Overview). . . . . . . . Cancer (Lectures 1 - 3).

. . • Glial cell proliferation. • Neuroprotection → copper ions → redox to reduce ROS.

. . A) PrPo/o mice show alterations in synaptic processes (Collinge et al., 1994).

. . 2241-2246 D) Human Molecular Genetics, 2005, vol. 14, No. 15 doi:10.1093/hmg/ddi228 Advance Access published on June 29, 2005 The prion gene is associated with human long-term memory Andreas Papassotiropoulosl *, M. Axel Wollmerl, Adriano Aguzzi2, Christoph Hockl Roger M. Nitschl and Dominique J.-F. de Quervain 1 IDivision of Psychiatry Research, University of Zurich, 8032 Zurich, Switzerland and 21nstitute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.

. . • PrPc-knock-out mice are resistant towards a scrapie infection.

. . Virino Hypothesis Protein-Only Hypothesis Co-Prion Hypothesis Nucleation-dependent Polymerization Model unlikely likely unlikely likely.

. . . PrP-Gen mRNA scrapie-spezifische Nukleinsäure Virino.

. . The EMBO Journal 25, 2674-2685 | @ European Molecular Biology Organization IAI Rights Reserved 0261418906 mvw.embojournaLorg EMBO JOURNAL Retrovirus infection strongly enhances scrapie infectivity release in cell culture.

. . Heterodimer Hypothesis Protein-Only Hypothesis (Griffith, Prusiner).

. . Conversion of PrPc to PrPSc is similar to the process of permanent waves (straight hair → curly/waves)..

. . • states that PrPSc must contain a small amount of host derived nucleic.

. . sporadic disease—slow nucleation FAS r SLOW FAST FAS' prPU prpC PrPSc (infectious agent=seed) O Chemistry & Biology, 1995.

. . The following statement/s are correct. • A) Prion proteins contain 3 alpha helices and 1 antiparallel beta.

. . Is BSE transmissible to. humans?.

. . Comparaison des lésions histologiques entre le macaque infecté par l'agent de I'ESB et le nouveau variant de MCJ chez l'homme Plaque floride (coupe de cerveau, coloration hémalun-éosine) Servke Neu•ovimW, DRM / ISV CEA, France..

. . Humanized mice are infectable with BSE which argues in favor of a transmission of BSE to humans Inoculation with BSE-prions Huprpo/o : Moprp+/+ (wild-typ FVB-mice) Inoculation with nvCJD-prions toovPrP+/+ MoPtrpo/o Huprp+/+ : Moprpo/o Huprpo/o : Moprp+/+ (wild-typ FVB-mice) incubation times 466* no symptoms after >540 days 228* 371* *Hill et al, Nature, 1997 "Scott et al, Proc. Natl. Acad. scl USA, 1999.

. . BSE is transmissible to humans and. results in the development of vCJD.

. . Genetic Frames Map of Prion Protein Open Reading Mutations causing Scrapie in mouse and sheep additional octa-repeats 86 morphism: does not directly result in a TSE but e development of a TSE (sometimes together with Does not cause BSE in ( only addition octa:repez tations) Do cause ••.additional fCJD in humans fa,nilial CJD.

. . 189 EI%K thogenic mutations cause IS or insertions in the region cause fCJD 1 OPRI m A117V diwzes umans Y145Stop 2 OPRD 51 P105L P105T TIN TIUK TIWR HIB7R T183A 0178N Q160Stop V2031 V2t01 E2t1Q Q212P M23 0217B A117A G142S IINM 1 OPRD Polymorphic variants G124G M129V E219K V161V H177H EI%E N171S TIET 02120 N173N R22BR Does not directly cause fCJD in humans but may affect the develo ment of TSE often to ether with other mutations Figure 5 Pathogenic mutations and m e uman pnon pro em. e pa ogemc mu ons assocn WI uman prion disease aro shown above the PrP coding sequence. consist of 1.2. or 4—0 octapeptide repeat insertions within the region between codons 51 and 91, a deletion of 2 octapeptide repeats, and various mutations causing missense amino acid substitutions. Point mutations are designated by the wild-type amino acid precmiing the codon number, followed by the mutant residue, using single- letter amino acid conventions. Polymorphic variants are shown tho PrP coding sequence. Deletion of one octapeptide repeat is not associated with disease (figure of Mr Jon Beck)..

. . Genetic marker for the Susceptibility to vCJD.

. . Which of the following statement/s. is/are wrong?.

. . Diagnosis of Prion Disorders. • Detection of Proteinase K resistant Prions (PrP27-30 kDa) in brain samples by Western Blotting or ELISA techniques..

. . Therapeutic intervention in prion. diseases. • No therapeutic is on the market for the.

. . Ludewigs, Vana. zerr & Webs Laminin re.tor HSPG (Core:.tor) • He mirneti:s • Pentcsan polysutfate Suramin scFv Full lengtl antibodies p.ti:ies (ß-sheet br—ker iPrP13) Modeled Prp•• • Phcephorotibate olipnucleoti&s • Congo red • Porprryrins, phthalocyaninæ • Anthracyclinæ (IDX) • Tetracycline' (tetracycline, • Polyene antibbti:s (AmB, MS8209) Figure 1. Sclematic vien of the propsed of actions of antiprion drugs. which are effetive and in Wtro. Heparan mimetics ard pentosan pdysulfate interfere with the Prp: and binding t' the 37E7-kDa laminin receptor ILRPLRI. Anthodiz directed against prF' or LRPtLR wth the PrFt binding to LRPtLR ct PrPS:. Many anti-transmissiöe sp:ngifctm (TSEI drugs er*t the PrFt-PrF5t con'.ersbn, such as phosphyothi:ate 019nudoti±s, Ccnp red, pyphyrins, phtalocyanires (e,dic anthrxyclines (101), tetrac',tlires and poWene Sne of them (eg„ p:vene antibiotics) are thought to interfere wth the PrP internalizatizn proce% The prFÆ—prpS: conæsion process might take pine either on the cell or within compartmmtsof the endo:yti: pathwax sch as endosomes, and Ceigner pepti&s might re.vse conformational charges of prF'c breaking *sheets. Suramin 3ggregates Frp: *sheet prF'C stucture, whi:h is no longer avai bble z template for convvsion to prpSc. HSPG: Heparan sulfate proto$,tane; PrP. Prion protein: scA'.• Sirglechain antibcdy. The inur of Prv- INMR stru:tu re) was fram 1"1). The of PrPSt appears courtesy of Fred E Cchen, Department Of Cellular Fharmacolcgy, Uni'*sityof California San Framiscc (UCSF),.

. . [Prion 20071; 02C071.•nJz Linienze Research Paper Anti-LRP/LR Antibody W3 Hampers Peripheral Prpsc Propagation in Scrapie Infected Mice Chantal Zuberl't Gerda Mitteregger2•t Claudia Patel Inga Zen: Hans A. Krehsthh1åt2 Stefan Weisslr* 'Litotr«ium fir fir fir Lu&ie cf Cerar TEZ Su'"ilzæ ABSTRACT We identified the 37kDa/67kDo lammin receptor ILRP/LR] o cell surfoce receptor Gr he cellular prion protein (PrPC) and the infecfious prion protein (PrPSCl- Recently, showed that anti-LRP/LR antibody W3 cured •crapie infected N2• •ells. Here, we deman- strate that W3 delivered by passive immunotronsfer into C57BL/6 mice reduced the Prec content in the spleen Eäenihconfly by 86%, demonstrating an impairment c; the peripheral PrPSc propagation. In addition, we observed 0 1 -a-fold increase in survival of onti-LRP/LR antibody W3 mice [mean survival of 31 days) compared io preimmune serum treated contre animals (mean survival •f 17 days). We conclude that the significant effect of onti-LRP/LR antibody on the reduction of peripheral PrPSc propagation might be due io the blockage o} the prion receptor LRP/LR which is required, as previously shown in vitro, fcr Presc propagation in vivo..

. . Estracellular space Cytosol receptor LR? LR oi 29 5 ucj•o O) "d to the g:oup oi (u its to space, Eave at 161-180 Ld ILEEoey to.

. . Feedstuffs F.rmers more UNITED Moms Strons sow re«arrh ehan* L EARN This Week in Avibusiness - August 7, 2021 @ Piglet nutrition scenarios for AGP USDA's octions on gene-ediied approvals ch.Uenged in court Vaccine may protect against chronic wasting disease Apr •zine Medicine 'heir nay. æ:ently in vet ire. i' in i' the arvid Smart Strategy Makes a Difference..

. . The Prion Protein and Disease. Cancer, Alzheimer‘s disease & Huntington‘s disease.

. . Cellular prion protein enhances metastatic gastric.

. . Franck Meslin,l Ahmed Hamai,l Ping Gao,2 Abdelali Jalil,l Nathalie Cahuzac,2 Salem Chouaib,l and Maryam Mehrpour 1.2 Ü753. Labcratrire des Turneurs Humaines. Interaction Cytotoxiques-Systenw butitut PRI 54. ViUejuiL and Of Of Apopttsis Cancer Biobgy. The State Key Laboratory of Biornembrane and Mernl:rane Biotechnolcgy. trutitute of Zoolcgy Beijing. China Cancer Res.

. . (McEwan et al. (Sylvan Pharmaceuticals), Poster Neuroprion Madrid 2008).

. . Which of the following statement/s is/are. correct?.

. . PrPc inhibits the -secretase cleavage of APP and thereby.

. . Journal of Alzheimer's Disease 49 (2016) 645—657 DOI 10.3233/JAD-150482 10S Press LRP/LR Antibody Mediated Rescuing of Amyloid-ß-lnduced Cytotoxicity 645 is Dependent on PrPC in Alzheimer's Disease Emma C. Pinnocka'l, Katarina Jovanovica'l, Maxine G. Pintoa, Eloise Ferreiraa, Bianca Da Costa Diasa, Clement Pennyb, Stefan Knackmussc, Uwe ReuschC, Melvyn Littlec, Hermann M. Schatzld and Stefan F.T. Weissa * aSchool of Molecular and Cell Biology, University of the Witwatersrand, Wits, Johannesburg, Republic of South Africa (RSA) Department of Internal Medicine, University of the Witwatersral , Johannesburg, Parktown, Republic of South Africa (RSA) CAffimed GmbH, Technologiepark, Heidelberg, Germanv Department of Comparative Biology & Experimental Medicme, University of Calgary, Calgary, AB, Canada.

. . Cellular prion protein protects neuronal cells from the.