TSECFAC: Analysis and function of 14-3-3 isoforms. Early diagnosis of Cruetzfeldt-Jakob disease

• Forschungsstelle: EU FRP
• Projektnummer: 98.0184
• Projekttitel Englisch: TSECFAC: Analysis and function of 14-3-3 isoforms. Early diagnosis of Cruetzfeldt-Jakob disease

Schlüsselwörter (Englisch)

Prions; BSE; Creutzfeldt-Jakob

Alternative Projektnummern (Englisch)

EU project number: BMH4CT986015

Forschungsprogramme (Englisch)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Kurzbeschreibung (Englisch)

See abstract

Partner und Internationale Organisationen (Englisch)

Coordinator: Klinisches Institut für Neurologie der Uni Wien (A)

Abstract (Englisch)

The role of plasminogen as a diagnostik marker for TSE`s
The protein-only hypothesis states that the causative agent of transmissible spongiform encephalopathies is PrPSc, a conformer of the cellular protein PrPC. Therefore, reagents differentiating between PrPC and PrPSc could be diagnostically useful.We have previously reported that the plasma protease plasminogen engages in a selective complex with disease-associated prion protein derived from brains of scrapie-infected mice. We have exploited this property to visualise PrPSc by plasminogen-mediated precipitation followed by western blotting [Fischer et al. 2000]. We have now explored whether these findings in mice can be extrapolated to other instances of transmissible spongiform encephalopathies.We linked human plasminogen (100 g) to 1 mL tosyl-activated paramagnetic Dynabeads M-280 (Dynal, Oslo, Norway). Brain tissues from a healthy mouse, a scrapie-affected mouse, pooled brains of Swiss non-affected cows, and brains of BSE-affected cows of various breeds were homogenised and tested for the presence of PrPSc.In all cases, plasminogen immobilised to magnetic beads captured PrPSc from each species after precipitation assay. In addition, we tested brain tissues (500 g) from several patients who died of sporadic Creutzfeldt-Jakob disease, Binswanger's disease, and Alzheimer's disease (diagnosed according to Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria; data not shown) with the prion affinity assay. In all assays done with homogenates of patients with CJD, plasminogen was able to precipitate PrPCJD, whereas no signal was detectable with homogenates of patients without CJD.Our surprising observation that plasminogen interacts with disease-associated prion protein from several species indicates that binding to plasminogen may be more frequent than previously postulated, and suggests that these findings may be suitable for exploitation as a diagnostic procedure.

Datenbankreferenzen (Englisch)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 98.0184