Down syndrome (DS), which is caused by triplication of human chromosome 21 (Hsa21), exhibits some physical signs of accelerated aging, such as graying hair, wrinkles and menopause at an unusually young age. Development of early-onset Alzheimer’s disease, which is frequently observed in adults with DS, is also suggested to occur due to accelerated aging of the brain. Several Hsa21 genes are suggested to be responsible for the accelerated aging in DS. In this review, we summarize these candidate genes and possible molecular mechanisms, and discuss the related key factors. In particular, we focus on copper, an essential trace element, as a key factor in the accelerated aging in DS. In addition, the physiological significance of brain copper accumulation in cognitive impairment is discussed. We herein provide our hypothesis on the copper dyshomeostasis-based pathophysiology of DS.
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Pharm. Bull."},{"@language":"ja","@value":"Ｂｉｏｌ． Ｐｈａｒｍ． Ｂｕｌｌ．"}],"dc:publisher":[{"@language":"en","@value":"The Pharmaceutical Society of Japan"},{"@language":"ja","@value":"公益社団法人 日本薬学会"}],"prism:publicationDate":"2023-09-01","prism:volume":"46","prism:number":"9","prism:startingPage":"1169","prism:endingPage":"1175"},"reviewed":"false","url":[{"@id":"https://www.jstage.jst.go.jp/article/bpb/46/9/46_b23-00131/_pdf"}],"availableAt":"2023-09-01","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Down%20syndrome","dc:title":"Down syndrome"},{"@id":"https://cir.nii.ac.jp/all?q=aging","dc:title":"aging"},{"@id":"https://cir.nii.ac.jp/all?q=oxidative%20stress","dc:title":"oxidative stress"},{"@id":"https://cir.nii.ac.jp/all?q=Alzheimer%E2%80%99s%20disease","dc:title":"Alzheimer’s disease"},{"@id":"https://cir.nii.ac.jp/all?q=Down%20syndrome","dc:title":"Down syndrome"},{"@id":"https://cir.nii.ac.jp/all?q=aging","dc:title":"aging"},{"@id":"https://cir.nii.ac.jp/all?q=oxidative%20stress","dc:title":"oxidative stress"},{"@id":"https://cir.nii.ac.jp/all?q=Alzheimer%E2%80%99s%20disease","dc:title":"Alzheimer’s disease"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040854882545329280","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22H04822"},{"@type":"JGN","@value":"JP22H04822"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY-22H04822/"}],"notation":[{"@language":"ja","@value":"ダウン症知的障害における初期エンドソーム破綻と銅蓄積"},{"@language":"en","@value":"Understanding the mechanisms underlying copper accumulation in the brain with Down syndrome"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050850412730695424","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ferroptosis is controlled by the coordinated transcriptional regulation of 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