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Inhibition of coppe...
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Gou, De HaiNortheastern University
(författare)
Inhibition of copper transporter 1 prevents α-synuclein pathology and alleviates nigrostriatal degeneration in AAV-based mouse model of Parkinson's disease
- Artikel/kapitelEngelska2021
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LIBRIS-ID:oai:lup.lub.lu.se:b214f19d-3a94-4eea-b860-676ffbfab285
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https://lup.lub.lu.se/record/b214f19d-3a94-4eea-b860-676ffbfab285URI
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https://doi.org/10.1016/j.redox.2020.101795DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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The formation of α-synuclein aggregates is a major pathological hallmark of Parkinson's disease. Copper promotes α-synuclein aggregation and toxicity in vitro. The level of copper and copper transporter 1, which is the only known high-affinity copper importer in the brain, decreases in the substantia nigra of Parkinson's disease patients. However, the relationship between copper, copper transporter 1 and α-synuclein pathology remains elusive. Here, we aim to decipher the molecular mechanisms of copper and copper transporter 1 underlying Parkinson's disease pathology. We employed yeast and mammalian cell models expressing human α-synuclein, where exogenous copper accelerated intracellular α-synuclein inclusions and silencing copper transporter 1 reduced α-synuclein aggregates in vitro, suggesting that copper transporter 1 might inhibit α-synuclein pathology. To study our hypothesis in vivo, we generated a new transgenic mouse model with copper transporter 1 conditional knocked-out specifically in dopaminergic neuron. Meanwhile, we unilaterally injected adeno-associated viral human-α-synuclein into the substantia nigra of these mice. Importantly, we found that copper transporter 1 deficiency significantly reduced S129-phosphorylation of α-synuclein, prevented dopaminergic neuronal loss, and alleviated motor dysfunction caused by α-synuclein overexpression in vivo. Overall, our data indicated that inhibition of copper transporter 1 alleviated α-synuclein mediated pathologies and provided a novel therapeutic strategy for Parkinson's disease and other synucleinopathies.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Huang, Ting TingNortheastern University
(författare)
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Li, WenLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang(Swepub:lu)med-wnl
(författare)
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Gao, Xin DiNortheastern University
(författare)
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Haikal, CarolineLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups(Swepub:lu)ca6087ha
(författare)
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Wang, Xin HeNortheastern University
(författare)
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Song, Dong YanNortheastern University
(författare)
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Liang, XinChongqing Medical University
(författare)
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Zhu, LinChongqing Medical University
(författare)
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Tang, YongChongqing Medical University
(författare)
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Ding, ChenNortheastern University
(författare)
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Li, Jia YiLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,Northeastern University,China Medical University, Shenyang(Swepub:lu)mphy-jli
(författare)
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Northeastern UniversityNeural plasticitet och reparation
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Redox Biology: Elsevier BV382213-2317
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Gou, De Hai
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Huang, Ting Ting
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Li, Wen
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Gao, Xin Di
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Haikal, Caroline
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Wang, Xin He
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visa fler...
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Song, Dong Yan
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Liang, Xin
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Zhu, Lin
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Tang, Yong
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Ding, Chen
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Li, Jia Yi
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- MEDICIN OCH HÄLSOVETENSKAP
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och Medicinska och f ...
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och Neurovetenskaper
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Redox Biology
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Lunds universitet