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学科主题基础医学
Magnesium Modulates Amyloid-beta Protein Precursor Trafficking and Processing
Yu, Jia1,2,3,4; Sun, Miao1,2,3; Chen, Zheng4; Lu, Jiangyang5; Liu, Yi1,2,3; Yang, Huan1,2,3; Zhou, Liang1,2,3; Xu, Xuemin6; Fan, Dongsheng1,7; Chui, Dehua1,2,3,7
关键词Alzheimer&Prime s Disease Amyloid-beta Amyloid-beta Protein Precursor Magnesium
刊名JOURNAL OF ALZHEIMERS DISEASE
2010
DOI10.3233/JAD-2010-091444
20期:4页:1091-1106
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]ALZHEIMERS-DISEASE BRAIN ; KINASE-C ; OXIDATIVE STRESS ; ALPHA-SECRETASE ; TRANSGENIC MICE ; CELL-SURFACE ; IN-VIVO ; MUTANT PRESENILIN-1 ; PEPTIDE PRODUCTION ; PRIMARY CULTURES
英文摘要

Alzheimer′s disease (AD), the most common form of dementia, is characterized by the presence of excessive deposits of aggregated amyloid-beta (A beta), which is derived from the amyloid-beta protein precursor (A beta PP) following processing by beta- and gamma-secretase. Metal elements are implicated in the pathophysiology of AD. Magnesium affects many biochemical mechanisms vital for neuronal properties and synaptic plasticity, and magnesium levels were reported to be decreased in various tissues including brain of AD patients. However, the exact role of magnesium in the neurodegenerative process of AD remains elusive. In this study, we investigated the effects of physiological (0.8 mM, as normal control), low (0-0.4 mM), and high (1.2-4.0 mM) concentrations of extracellular magnesium ([Mg(2+)](o)) on A beta PP processing and A beta secretion. Here we show the effects of varying [Mg(2+)](o) on A beta PP processing is time-and dose-dependent. After 24 h treatment, high [Mg(2+)](o) increased C-terminal fragment-alpha (CTF alpha) levels and soluble alpha-secretase cleaved A beta PP (sA beta PP alpha) release via enhancing retention of A beta PP on plasma membrane. In contrast, low [Mg(2+)](o) enhanced CTF beta accumulation and A beta secretion, and reduced cell surface A beta PP level. Varying [Mg(2+)](o) did not alter protein contents of full length A beta PP. However, decreased total intracellular magnesium level by magnesium deprivation over 24 hr impaired cell viability. Normal A beta PP processing could be restored when magnesium was adjusted back to physiological concentration. These data demonstrate that A beta PP processing can be modulated by magnesium and at high [Mg(2+)](o), A beta PP processing favors the alpha-secretase cleavage pathway. Our findings suggest that supplementation of magnesium has a therapeutic potential for preventing AD.

语种英语
WOS记录号WOS:000279539500014
项目编号30570533 ; 30670414 ; 30973145 ; 2006CB500705 ; 0060102A4031
资助机构National Natural Science Foundation of China (NSFC) ; National High Technology Research and Development Program of China (973 Program) ; National High Technology Research and Development Program of China (863 Program)
引用统计
被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61012
专题北京大学基础医学院_神经生物学系
北京大学第一临床医学院_肾脏内科
北京大学第二临床医学院_超声影像科
北京大学第三临床医学院_神经内科
作者单位1.Beijing Geriatr Hosp, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Key Lab Neurosci,Minist Educ, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Minist Publ Hlth, Beijing 100191, Peoples R China
5.Gen Hosp PLA, Affiliated Hosp 1, Dept Pathol, Beijing, Peoples R China
6.Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37901 USA
7.Peking Univ, Dept Neurol, Hosp 3, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Yu, Jia,Sun, Miao,Chen, Zheng,et al. Magnesium Modulates Amyloid-beta Protein Precursor Trafficking and Processing[J]. JOURNAL OF ALZHEIMERS DISEASE,2010,20(4):1091-1106.
APA Yu, Jia.,Sun, Miao.,Chen, Zheng.,Lu, Jiangyang.,Liu, Yi.,...&Chui, Dehua.(2010).Magnesium Modulates Amyloid-beta Protein Precursor Trafficking and Processing.JOURNAL OF ALZHEIMERS DISEASE,20(4),1091-1106.
MLA Yu, Jia,et al."Magnesium Modulates Amyloid-beta Protein Precursor Trafficking and Processing".JOURNAL OF ALZHEIMERS DISEASE 20.4(2010):1091-1106.
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