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Showing posts with the label misfolded proteins

Dominant prion mutants induce curing through pathways that promote chaperone-mediated disaggregation

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Protein misfolding underlies many neurodegenerative diseases, including the transmissible spongiform encephalopathies (prion diseases). Although cells typically recognize and process misfolded proteins, prion proteins evade protective measures by forming stable, self-replicating aggregates. However, coexpression of dominant-negative prion mutants can overcome aggregate accumulation and disease progression through currently unknown pathways. Here we determine the mechanisms by which two mutants of the Saccharomyces cerevisiae Sup35 protein cure the [ PSI + ] prion. We show that both mutants incorporate into wild-type aggregates and alter their physical properties in different ways, diminishing either their assembly rate or their thermodynamic stability. Whereas wild-type aggregates are recalcitrant to cellular intervention, mixed aggregates are disassembled by the molecular chaperone Hsp104 . Thus, rather than simply blocking misfolding, dominant-negative prion mutants target multiple...

Two interesting bids on the billboard II

The story of Sanofi-Aventis '  hostile bid for Genzyme Corp  continues,  Chief Executive Henri Termeer said he is willing to sell the company he built up over 25 years, but not for $69 a share.  In an interview with Reuters , Termeer said it was unlikely that French drugmaker Sanofi-Aventis SA would go hostile with its $18.5 billion bid and that the two sides had a good chance of coming to terms, though negotiations could last months. On Monday, the Cambridge, Massachusetts-based biotech company rejected Sanofi's bid of $69 a share. Sanofi has hinted it may take its offer directly to Genzyme shareholders if the company refuses to enter discussions based on its current offer.  Genzyme, in turn, is working its way through a manufacturing crisis that has lead to shortages of two of its biggest-selling products. Genzyme shares closed at $70.11 on Tuesday. Investors and industry analysts polled by Reuters have said a deal could be clinched at close to $78 per share....