By suppressing the expression of anterior pharynx-defective-1α and -1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice

Xin Yu, Pei Pei Guan, Jing Wen Guo, Yue Wang, Long Long Cao, Guo Biao Xu, K Konstantopoulos, Zhan You Wang, Pu Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is associated with a magnesium ion (Mg2+) deficit in the serum or brain. However, the mechanisms regulating the roles of Mg2+ in the pathologic condition of AD remain unknown. We studied whether brain Mg2+ can decrease β-amyloid (Aβ) deposition and ameliorate the cognitive decline in a model of AD, the APPswe/PS1DE9 transgenic (Tg) mouse. We used a recently developed compound, magnesium-L-threonate (MgT), for a treatment that resulted in enhanced clearance of Aβ in an anterior pharynx-defective (APH)-1α/-1β-dependent manner. To further explore how MgT treatment inhibits cognitive decline in APP/PS1 Tg mice, the critical molecules for amyloid precursor protein (APP) cleavage and signaling pathways were investigated. In neurons, ERK1/2 and PPARγ signaling pathways were activated by MgT treatment, which in turn suppressed (by >80%) the expression of APH-1α/-1β, which is responsible for the deposition of Aβ and potentially contributes to the memory deficit that occurs in AD. More important, Aβ oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1α/-1β (by >2.5-fold), which enhances the g-cleavage of APP and Ab deposition during AD progression. These findings provide new insights into the mechanisms of AD progression and are instrumental for developing better strategies to combat the disease.

Original languageEnglish (US)
Pages (from-to)5044-5058
Number of pages15
JournalFASEB Journal
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2015

Keywords

  • Alzheimer's disease
  • Cerebrospinal fluid
  • ERK1/2
  • Magnesium-L-threonate
  • PPARγ

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

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