Lang, M. L., Wang, L., Fan, Q. W., Xiao, G. R., Wang, X. X., Zhong, Y., Zhou, B. (April 2012) Genetic Inhibition of Solute-Linked Carrier 39 Family Transporter 1 Ameliorates A beta Pathology in a Drosophila Model of Alzheimer's Disease. PLoS Genetics, 8 (4). pp. 623-639. ISSN 1553-7390
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Abstract
The aggregation or oligomerization of amyloid-beta (A beta) peptide is thought to be the primary causative event in pathogenesis of Alzheimer's disease (AD). Considerable in vitro evidence indicates that the aggregation/oligomerization of A beta is promoted in the presence of Zn; however, the functional role of Zn in AD pathogenesis is still not well clarified in vivo. Zn is imported into the brain mainly through the solute-linked carrier (Slc) 39 family transporters. Using a genetically tractable Drosophila model, we found that the expression of dZip1, the orthologue of human Slc39 family transporter hZip1 in Drosophila, was altered in the brains of A beta 42-expressing flies, and Zn homeostasis could be modulated by forcible dZip1 expression changes. An array of phenotypes associated with A beta expression could be modified by altering dZip1 expression. Importantly, A beta 42 fibril deposits as well as its SDS-soluble form were dramatically reduced upon dZip1 inhibition, resulting in less neurodegeneration, significantly improved cognitive performance, and prolonged lifespan of the A beta 42-transgenic lies. These findings suggest that zinc contributes significantly to the A beta pathology, and manipulation of zinc transporters in AD brains may provide a novel therapeutic strategy.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | amyloid plaques transgenic mice zinc ions aggregation peptide copper brain imbalances memory iron |
| Subjects: | diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease diseases & disorders > mental disorders > delirium dementia cognitive disorders diseases & disorders organism description > animal > insect > Drosophila organism description > animal > insect |
| CSHL Authors: | |
| Communities: | CSHL labs > Zhong lab |
| Depositing User: | Matt Covey |
| Date: | April 2012 |
| Date Deposited: | 30 Jan 2013 17:09 |
| Last Modified: | 30 May 2014 16:51 |
| PMCID: | PMC3343105 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/26985 |
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