The Effect of Zinc on Amyloid beta-protein Assembly and Toxicity: a Mechanistic Investigation

Inna Solomonov, Irit Sagi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Neurotoxic assemblies of amyloid beta-protein (A beta) are widely believed to be the cause for Alzheimer's disease (AD). Therefore, understanding the factors and mechanisms that control, modulate, and inhibit formation of these assemblies is crucial for the development of therapeutic intervention of AD. This information also can contribute significantly to our understanding of the mechanisms of other amyloidosis diseases, such as Parkinson's disease, Huntington's disease, type 2 diabetes, amyotrophic lateral sclerosis (Lou Gehrig's disease) and prion diseases (e.g. Mad Cow disease). We have developed a multidisciplinary experimental strategy to study structural and dynamic mechanistic aspects that underlie the A beta assembly process. Utilizing this strategy, we explored the molecular basis leading to the perturbation of the A beta assembly process by divalent metal ions, mainly Zn2+ ions. Using Zn2+ as reaction physiological relevant probes, it was demonstrated that Zn2+ rapidly (milliseconds) induce self-assembly of A beta aggregates and stabilize them in a manner that prevents formation of A beta fibrils. Importantly, the early-formed intermediates are substantially more neurotoxic than fibrils. Our results suggest that relevant A beta modulators should be targeted against the rapidly evolved intermediate states of A beta assembly. The design of such modulators is challenging, as they have to compete with different natural mediators (such as Zn2+) of A beta aggregation, which diverse A beta assemblies in both specific and nonspecific manners.

Original languageEnglish
Title of host publicationInternational Conference of Computational Methods in Sciences and Engineering (ICCMSE 2014)
EditorsTE Simos, Z Kalogiratou, T Monovasilis
PublisherAmerican Institute of Physics
Pages121-124
Number of pages4
ISBN (Electronic)9780735412552
DOIs
StatePublished - 2014
EventInternational Conference of Computational Methods in Sciences and Engineering 2014 (ICCMSE) - Athens, GREECE, Athens, Greece
Duration: 4 Apr 20147 Apr 2014

Publication series

NameAIP Conference Proceedings
Volume1618
ISSN (Print)0094-243X

Conference

ConferenceInternational Conference of Computational Methods in Sciences and Engineering 2014 (ICCMSE)
Country/TerritoryGreece
CityAthens
Period4/04/147/04/14

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy

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