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Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model

Zinc is a fundamental trace element essential for numerous biological processes, and zinc homeostasis is regulated by the Zrt-/Irt-like protein (ZIP) and zinc transporter (ZnT) families. ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER) and transports zinc into these org...

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Autores principales: Lee, Banseok, Choi, Byoungyun, Park, Youngjae, Jang, Seokhui, Yuan, Chunyu, Lim, Chaejin, Lee, Jang Ho, Song, Gyun Jee, Cho, Kyoung Sang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569493/
https://www.ncbi.nlm.nih.gov/pubmed/36233134
http://dx.doi.org/10.3390/ijms231911832
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author Lee, Banseok
Choi, Byoungyun
Park, Youngjae
Jang, Seokhui
Yuan, Chunyu
Lim, Chaejin
Lee, Jang Ho
Song, Gyun Jee
Cho, Kyoung Sang
author_facet Lee, Banseok
Choi, Byoungyun
Park, Youngjae
Jang, Seokhui
Yuan, Chunyu
Lim, Chaejin
Lee, Jang Ho
Song, Gyun Jee
Cho, Kyoung Sang
author_sort Lee, Banseok
collection PubMed
description Zinc is a fundamental trace element essential for numerous biological processes, and zinc homeostasis is regulated by the Zrt-/Irt-like protein (ZIP) and zinc transporter (ZnT) families. ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER) and transports zinc into these organelles. Although previous studies have reported the role of zinc in animal physiology, little is known about the importance of zinc in the Golgi apparatus and ER in animal development and neurodegenerative diseases. In this study, we demonstrated that ZnT86D, a Drosophila ortholog of ZnT7, plays a pivotal role in the neurodevelopment and pathogenesis of Alzheimer disease (AD). When ZnT86D was silenced in neurons, the embryo-to-adult survival rate, locomotor activity, and lifespan were dramatically reduced. The toxic phenotypes were accompanied by abnormal neurogenesis and neuronal cell death. Furthermore, knockdown of ZnT86D in the neurons of a Drosophila AD model increased apoptosis and exacerbated neurodegeneration without significant changes in the deposition of amyloid beta plaques and susceptibility to oxidative stress. Taken together, our results suggest that an appropriate distribution of zinc in the Golgi apparatus and ER is important for neuronal development and neuroprotection and that ZnT7 is a potential protective factor against AD.
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spelling pubmed-95694932022-10-17 Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model Lee, Banseok Choi, Byoungyun Park, Youngjae Jang, Seokhui Yuan, Chunyu Lim, Chaejin Lee, Jang Ho Song, Gyun Jee Cho, Kyoung Sang Int J Mol Sci Article Zinc is a fundamental trace element essential for numerous biological processes, and zinc homeostasis is regulated by the Zrt-/Irt-like protein (ZIP) and zinc transporter (ZnT) families. ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER) and transports zinc into these organelles. Although previous studies have reported the role of zinc in animal physiology, little is known about the importance of zinc in the Golgi apparatus and ER in animal development and neurodegenerative diseases. In this study, we demonstrated that ZnT86D, a Drosophila ortholog of ZnT7, plays a pivotal role in the neurodevelopment and pathogenesis of Alzheimer disease (AD). When ZnT86D was silenced in neurons, the embryo-to-adult survival rate, locomotor activity, and lifespan were dramatically reduced. The toxic phenotypes were accompanied by abnormal neurogenesis and neuronal cell death. Furthermore, knockdown of ZnT86D in the neurons of a Drosophila AD model increased apoptosis and exacerbated neurodegeneration without significant changes in the deposition of amyloid beta plaques and susceptibility to oxidative stress. Taken together, our results suggest that an appropriate distribution of zinc in the Golgi apparatus and ER is important for neuronal development and neuroprotection and that ZnT7 is a potential protective factor against AD. MDPI 2022-10-05 /pmc/articles/PMC9569493/ /pubmed/36233134 http://dx.doi.org/10.3390/ijms231911832 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Banseok
Choi, Byoungyun
Park, Youngjae
Jang, Seokhui
Yuan, Chunyu
Lim, Chaejin
Lee, Jang Ho
Song, Gyun Jee
Cho, Kyoung Sang
Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model
title Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model
title_full Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model
title_fullStr Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model
title_full_unstemmed Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model
title_short Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model
title_sort roles of znt86d in neurodevelopment and pathogenesis of alzheimer disease in a drosophila melanogaster model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569493/
https://www.ncbi.nlm.nih.gov/pubmed/36233134
http://dx.doi.org/10.3390/ijms231911832
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