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SUMMARY:Kinetic Insights into amyloid-β metal ion interactions and implic
 ations for AD. - Dr Liming Ying\, Imperial College London
DTSTART:20171206T103000Z
DTEND:20171206T113000Z
UID:TALK94072@talks.cam.ac.uk
CONTACT:Patrick Flagmeier
DESCRIPTION:The kinetics of the interactions between amyloid-β (Aβ) and 
 metal ions are crucial to understanding the physiological and pathological
  roles of Aβ in the normal brain and in Alzheimer’s disease. Using the 
 quenching of a fluorescent probe by Cu(II)\, we have elucidated the kineti
 c mechanism of Aβ/Cu(II) interactions in physiologically relevant conditi
 ons. FAD mutations and phosphorylation of Aβ were found to modulate the k
 inetics of interconversion between the two Cu(II) coordination modes and e
 nhance copper-bridged dimer formation.  Further computational reaction-dif
 fusion simulations of the interactions of synaptically released metal ions
  with Aβ indicated that up to a third of Aβ is Cu(II)-bound under repeti
 tive metal ion release\, while any other Aβ-metal complexes (including A
 β-Zn) are insignificant. In addition\, the timescale of redox cycling of 
 the Aβ-Cu complex were determined and found biologically relevant. These 
 results suggest that targeting specific interactions between Cu(II) and A
 β may be a viable option in drug development efforts for early stages of 
 AD.
LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre
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