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学科主题: 基础医学
题名:
Magnesium Modulates Amyloid-beta Protein Precursor Trafficking and Processing
作者: 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
发表日期: 2010
DOI: 10.3233/JAD-2010-091444
卷: 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
所属项目编号: 30570533 ; 30670414 ; 30973145 ; 2006CB500705 ; 0060102A4031
项目资助者: 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)
WOS记录号: WOS:000279539500014
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61012
Appears in Collections:基础医学院_神经生物学系_期刊论文

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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

Recommended Citation:
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.
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