We defined the mechanism of inhibition of PrP conversion by curcumin, the active ingredient of spice turmeric. We showed binding of curcumin to both toxic ß-oligomers as well as to amyloid fibrils. Curcumin bound to partially unfolded ?-form PrP, formed at acidic pH, but not to the native PrP. This is the first description of a nontoxic compound of natural source binding to the partially unfolded intermediate of the prion protein. Our results are important for potential use of curcumin and its derivates with improved pharmacological features for diagnosis and therapy of amyloid diseases.
COBISS.SI-ID: 3896346
The structural conversion of prion protein occurring in prion disease is not well characterized, especially due to the lack of knowledge on the structure of pathological form, PrPSc. Thus a comprehensive set of well characterized antibodies directed against various epitopes on PrP might prove invaluable in obtaining structural information on PrPSc and characterization of prion strains. We also show that this antibody set can be used in various experimental platforms, which even broadens its applicability in basic research and diagnostics.
COBISS.SI-ID: 4096794
We report a new method for the synthesis of biarsenical reagents, which are then used to monitor murine PrP (mPrP) misfolding. We introduced tetracysteine (TC) tags which bind biarsenical compounds into mPrP and devised a quantitative protease-free method for following PrP conversion, based on the ability of the biarsenical reagent to differentiate between the monomeric and fibrilized form of TC-tagged PrP, and showed that TC-tagged mPrP could be detected on cells, thereby expanding the potential use of this method for the detection and study of conformational diseases.
COBISS.SI-ID: 4377626
Despite three awarded Nobel prizes related to prion diseases the key unanswered question is the identification of structural segments that undergo rearrangement in PrP conversion. We tethered the selected structural segments of PrP by disulfide tethers and following their effect on conversion. In contrast to most published structural models our results showed that the majority of secondary structure elements remain intact, which is important in designing new therapies. Krka Prize was awarded for PhD thesis describing these results, publication is in preparation (enclosed).
COBISS.SI-ID: 3808538
JERALA, Roman. The mysteries and misdeeds of the prion protein : [invited lecture at] PENS summer school "Novel molecular strategies to treat neurodegenerative diseases". Ofir [Portugal], July 8-15, 2007. Prof. Jerala presented the current state of the art and project group's results on prion diseases.
COBISS.SI-ID: 3769626