title: 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.
abstract: Alzheimer's disease (AD) is associated with a magnesium ion (Mg(2+)) deficit in the serum or brain. However, the mechanisms regulating the roles of Mg(2+) in the pathologic condition of AD remain unknown. We studied whether brain Mg(2+) 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 γ-cleavage of APP and Aβ 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.
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Xin
authors: X
authors: Yu
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Pei-Pei
authors: PP
authors: Guan
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Jing-Wen
authors: JW
authors: Guo
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Yue
authors: Y
authors: Wang
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Long-Long
authors: LL
authors: Cao
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Guo-Biao
authors: GB
authors: Xu
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA.
authors: Konstantinos
authors: K
authors: Konstantopoulos
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA wangpu@mail.neu.edu.cn wangzy@mail.neu.edu.cn.
authors: Zhan-You
authors: ZY
authors: Wang
authors: *College of Life and Health Sciences, Northeastern University, Shenyang, China; and Department of Chemical and Biomolecular Engineering, Department of Biomedical Engineering, Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins Physical Sciences-Oncology Center, and Center of Cancer Nanotechnology Excellence, The Johns Hopkins University, Baltimore, Maryland, USA wangpu@mail.neu.edu.cn wangzy@mail.neu.edu.cn.
authors: Pu
authors: P
authors: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D003072:Cognition Disorders / Q000517:prevention & control*; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1; C580804:presenilin 1, mouse; D010450:Endopeptidases; C498194:Aph1a protein, mouse; C498195:Aph1b protein, mouse; D008274:Magnesium
keywords: Alzheimer’s disease; ERK1/2; PPARγ; cerebrospinal fluid; magnesium-l-threonate