BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Copper 2+ binding to Aβ accelerates fiber growth and enhances neu
 rotoxicity. - John H Viles\, Queen Mary\, University of London
DTSTART:20111020T130000Z
DTEND:20111020T140000Z
UID:TALK33532@talks.cam.ac.uk
CONTACT:Damian Crowther
DESCRIPTION:Although Cu2+ ions are found concentrated within senile plaque
 s of Alzheimer’s disease patients directly bound to A and in vivo stu
 dies have shown that impaired copper homeostasis enhances the toxic effect
 s of A.  A role for Cu2+ ions in Alzheimer’s disease (AD) is often di
 sputed\, as it is believed that Cu2+ ions have a relatively low affinity f
 or A and promote non-toxic amorphous aggregates of amyloid- (A
 . In contrast with currently held opinion\, we show that Cu2+ ions in fact
  doubles the rate of production of amyloid fibres\, accelerating both the 
 nucleation and elongation of fibre formation. We further show that Cu2+ io
 ns bound to A are consistently more toxic to neuronal cells than A i
 n the absence of Cu2+ ions. The affinity of Cu2+ for A is highly disput
 ed. Our competition studies indicate a dissociation constant of 10-11 M\, 
 at pH 7.4\, for both fibrillar and monomeric forms. Electron paramagnetic 
 resonance studies (EPR) suggest a dynamic view of the tetragonal Cu2+ comp
 lex creating an ensemble of coordination geometries in exchange between ea
 ch other. An active role for Cu2+ ions in accelerating fibre formation and
  promoting cell death coupled with the high affinity of Cu2+ for A\, su
 ggests impaired copper homeostasis could be a risk factor in Alzheimer’s
  disease.   \n\n[1] Substoichiometric Levels of Cu2+ Ions Accelerate the K
 inetics of Fiber Formation and Promote Cell Toxicity of Amyloid-β from Al
 zheimer Disease. Claire J. Sarell\, Shane R. Wilkinson and John H. Viles (
 2010) J Biol Chem 285\, 41533-41540.\n\n[2] Cu(II) binding to amyloid-beta
  fibrils of Alzheimer’s Disease reveals a pico-molar affinity. CJ  Sarel
 l\, CD Syme\, SEJ Rigby and *Viles JH (2009) Biochemistry 48\, 4388-402\n\
 n[3] Copper binding to the amyloid-beta (Aβ) peptide associated with Alzh
 eimer’s disease.   \nCD Syme\, RC Nadal\, SEJ Rigby and *Viles JH (2004)
  J Biol Chem. 279\, 18169-18177\n
LOCATION:Bateson Room\, Department of Genetics\, Downing Site
END:VEVENT
END:VCALENDAR