SH2B1 is Involved in the Accumulation of Amyloid-beta(42) in Alzheimer's Disease
文献类型：期刊论文
| 作者 | Shen, Yijun2,3; Xia, Yiling2,3; Meng, Shiquan3; Lim, Nastasia K. H.3,4; Wang, Wenan1,2; Huang, Fude3 |
| 刊名 | JOURNAL OF ALZHEIMERS DISEASE
 |
| 出版日期 | 2017 |
| 卷号 | 55期号:2页码:835-847 |
| 关键词 | Alzheimer's disease amyloid-beta accumulation diabetes SH2B1 protein |
| ISSN号 | 1387-2877 |
| DOI | 10.3233/JAD-160233 |
| 文献子类 | Article |
| 英文摘要 | Alzheimer's disease (AD) is characterized by deficits in learning and memory abilities, as well as pathological changes of amyloid-beta (A beta) plaque and neurofibrillary tangle formation in the brain. Insulin has been identified as a modulator of the neuronal pathways involved in learning and memory, and is also implicated as a modulator of A beta and tau metabolism. Disrupted insulin signaling pathways are evident in AD patients and it is understood that type 2 diabetes can increase the risk of developing AD, suggesting a possible link between metabolic disorders and neurodegeneration. SH2B1 is a key protein in the insulin signaling pathway involved in regulating the activity of the insulin receptor. To further identify the role of the insulin signaling pathway in the pathology of AD, SH2B (dSH2B homologue in flies) in neurons was partially knocked out or overexpressed in an AD Drosophila model expressing A beta(42). Partial knockout of neuronal SH2B in the A beta(42)-expressing Drosophila had a detrimental effect on mobility and neurotransmission, and increased levels and intraneuronal accumulation of A beta(42), as assessed by ELISA and immunostaining. Alternatively, partial overexpression of neuronal SH2B in the A beta(42)-expressing Drosophila improved lifespan, mobility, and neurotransmission, as well as decreased levels and intraneuronal accumulation of A beta(42). Thus, SH2B1 may be an upstream modulator of A beta metabolism, acting to inhibit A beta accumulation, and has a role in the pathogenesis of AD. SH2B1 may therefore have potential as a therapeutic target for this common form of dementia. |
| WOS关键词 | INSULIN-DEGRADING ENZYME ; INTRANASAL INSULIN ; DROSOPHILA MODEL ; GLUCOSE-LEVELS ; BETA ; DEMENTIA ; MEMORY ; EXPRESSION ; PATHOLOGY ; RISK |
| 资助项目 | National Natural Science Foundation of China[81371400] ; National Natural Science Foundation of China[81071026] ; National Basic Research Development Program of China[2013CB530900] ; support for key discipline of Chongming County[00000000] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000389695700034 |
| 出版者 | IOS PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275753]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Wenan; Huang, Fude |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Neurol,Chongming Branch, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Neurol, Shanghai 202150, Peoples R China; 3.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201210, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Shen, Yijun,Xia, Yiling,Meng, Shiquan,et al. SH2B1 is Involved in the Accumulation of Amyloid-beta(42) in Alzheimer's Disease[J]. JOURNAL OF ALZHEIMERS DISEASE,2017,55(2):835-847. |
| APA | Shen, Yijun,Xia, Yiling,Meng, Shiquan,Lim, Nastasia K. H.,Wang, Wenan,&Huang, Fude.(2017).SH2B1 is Involved in the Accumulation of Amyloid-beta(42) in Alzheimer's Disease.JOURNAL OF ALZHEIMERS DISEASE,55(2),835-847. |
| MLA | Shen, Yijun,et al."SH2B1 is Involved in the Accumulation of Amyloid-beta(42) in Alzheimer's Disease".JOURNAL OF ALZHEIMERS DISEASE 55.2(2017):835-847. |
入库方式： OAI收割
来源：上海药物研究所
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