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SUMMARY:Systematic development of small molecules against Aβ aggregation 
 - Michele  Vendruscolo ( Dept. of Chemistry)
DTSTART:20171207T120000Z
DTEND:20171207T130000Z
UID:TALK95845@talks.cam.ac.uk
CONTACT:Alex Leonard
DESCRIPTION:The aggregation of the 42-residue form of the amyloid-beta pep
 tide \n(Abeta42) is a pivotal event in Alzheimer's disease (AD). The use o
 f \nchemical kinetics has recently enabled highly accurate quantifications
  \nof the effects of small molecules on specific microscopic steps in \nAb
 eta42 aggregation. I will explain how we have exploited this approach \nto
  develop a rational drug discovery strategy against Abeta42 \naggregation 
 that uses as a read-out the changes in the nucleation and \nelongation rat
 e constants caused by candidate small molecules. We have \nthus identified
  a pool of compounds that target specific microscopic \nsteps in Abeta42 a
 ggregation. We have then tested further these small \nmolecules in human c
 erebrospinal fluid and in a Caenorhabditis elegans \nmodel of AD. These re
 sults show that this strategy represents a powerful \napproach to identify
  systematically small molecule lead compounds\, thus \noffering an appeali
 ng opportunity to reduce the attrition problem in \ndrug discovery.
LOCATION:TCM Seminar room\, 530 Mott building
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