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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Mol+Neurosci
2018 ; 11
(ä): 172
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Magnesium Ions Inhibit the Expression of Tumor Necrosis Factor ? and the Activity
of ?-Secretase in a ?-Amyloid Protein-Dependent Mechanism in APP/PS1 Transgenic
Mice
#MMPMID29899688
Yu X
; Guan PP
; Zhu D
; Liang YY
; Wang T
; Wang ZY
; Wang P
Front Mol Neurosci
2018[]; 11
(ä): 172
PMID29899688
show ga
Alzheimer's disease (AD) is a neurodegenerative disease characterized by
cognitive impairment. The neuropathological features of AD are the aggregation of
extracellular amyloid ?-protein (A?) and tau phosphorylation. Recently, AD was
found to be associated with magnesium ion (Mg(2+)) deficit and tumor necrosis
factor-alpha (TNF-?) elevation in the serum or brains of AD patients. To study
the relationship between Mg(2+) and TNF-?, we used human- or mouse-derived glial
and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo
experimental models, respectively. Our data demonstrates that
magnesium-L-threonate (MgT) can decrease the expression of TNF-? by restoring the
levels of Mg(2+) in glial cells. In addition, PI3-K/AKT and NF-?B signals play
critical roles in mediating the effects of Mg(2+) on suppressing the expression
of TNF-?. In neurons, Mg(2+) elevation showed similar suppressive effects on the
expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a
PI3-K/AKT and NF-?B-dependent mechanism. As the major components of ?-secretase,
overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the
synthesis of A?, which in turn activates TNF-? in glial cells. Reciprocally,
TNF-? stimulates the expression of PEN2 and NCT in neurons. The crosstalk between
TNF-? and A? in glial cells and neurons could ultimately aggravate the
development and progression of AD.