Genetic inhibition of solute-linked carrier 39 family transporter 1 ameliorates aβ pathology in a Drosophila model of Alzheimer's disease.

PLoS Genetics
Minglin LangBing Zhou

Abstract

The aggregation or oligomerization of amyloid-β (Aβ) peptide is thought to be the primary causative event in the pathogenesis of Alzheimer's disease (AD). Considerable in vitro evidence indicates that the aggregation/oligomerization of Aβ 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 Aβ42-expressing flies, and Zn homeostasis could be modulated by forcible dZip1 expression changes. An array of phenotypes associated with Aβ expression could be modified by altering dZip1 expression. Importantly, Aβ42 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 Aβ42-transgenic flies. These findings suggest that zinc contributes significantly to the Aβ pathology, and manipulation of zinc transporters in AD brains may provide a...Continue Reading

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Citations

Nov 19, 2013·Pharmacogenomics·Calvin LeungG Gregory Neely
Nov 26, 2013·Molecular Neurodegeneration·Katja PrüßingJörg B Schulz
Jul 27, 2012·Metallomics : Integrated Biometal Science·Giuseppe GrassoEnrico Rizzarelli
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Sep 26, 2015·Cellular and Molecular Life Sciences : CMLS·Yunpeng HuangBing Zhou
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Jan 10, 2018·Frontiers in Genetics·Juan A Navarro, Stephan Schneuwly
Apr 25, 2020·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Asli Ayka, Ahmet Özer Şehirli
Jan 18, 2019·Communications Biology·Yunpeng HuangBing Zhou
Feb 6, 2020·International Journal of Molecular Sciences·Youngjae JeonKyoung Sang Cho
Dec 11, 2019·Molecular Brain·Yingshuo XuMinglin Lang
Jan 12, 2020·Communications Biology·Yunpeng HuangBing Zhou
May 4, 2016·Archives of Biochemistry and Biophysics·Guiran Xiao, Bing Zhou
May 29, 2018·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Weiwei MaYi Zhong

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Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

ImagJ
BLAST
Prism
TM
HMM
LSM 510
GraphPad

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