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.
New research in The FASEB Journal suggests that
magnesium ions may slow the progression of the
disease by disrupting the development of amyloid
plaques.
New research published in the December 2015 issue of
The FASEB Journal, shows that in mouse models of the
disease oral administration of magnesium-L-threonate
(MgT) alleviated cognitive decline by suppressing
the Aß deposition in amyloid plaques in an
APH-1a/1ß-dependent manner. Although questions still
remain about how MgT permeates the blood-brain
barrier, the work suggests that scientists may have
found the key to a new series of Alzheimer's disease
treatments. Specifically, they show that magnesium
ions target pharynx defective (APH)-APH-1a/1ß-suppressing
the A? deposition in amyloid plaques in an anterior
pharynx defective (APH)-APH-1a/1ß-dependent manner.
"We hope that our findings will help improve
clinical practice pertinent to the optimal
administration of Mg2+ for delaying or even
preventing the onset of AD," said Pu Wang, Ph.D., a
researcher involved in the work from the Department
of Life Science and Health at Shenyang, Liaoning,
China. "Moreover, we hope to extend our experimental
models to other disorders such as severe
craniocerebral injury, bronchial asthma, chronic
pulmonary heart disease, arrhythmia and myocardial
necrosis, etc. and identify more targets of Mg2+ and
strategies for treating these disorders."
To make this discovery, Wang and colleagues used two
groups of mice. The first group consisted of normal
mice. The second group consisted of mice
overexpressing a gene that enhances the expression
of APH-APH-1a/1ß and the production of Aß, while
also decreasing the Mg2+ influx in the brain,
especially in cerebrospinal fluid. When researchers
restored Mg2+ in the cerebrospinal fluid of the
genetically modified mice, the highly induced
APH-APH-1a/1ß expression was inhibited, which
resulted in alleviating Aß aggregation and cognitive
decline. Although the researchers did not find any
direct evidence showing that MgT was able to
penetrate the blood brain barrier, their findings
showed elevated levels of Mg2+ in the brains of the
genetically modified mice--sufficient for inhibiting
the development of Alzheimer's disease.
"The good news about this work is that if it holds
up in humans, magnesium is a common element that is
readily available," said Gerald Weissmann, M.D.,
Editor-in-Chief of The FASEB Journal. "The bad news,
of course, is that what works in mice does not
always turn out so well in people. At the same time,
even if magnesium ions do not work out for people
with Alzheimer's, this report will help researchers
learn how to slow the development amyloid plaques, a
hallmark of the disease."
For more information
Xin Yu, Pei-Pei Guan, Jing-Wen Guo, Yue Wang,
Long-Long Cao, Guo-Biao Xu, Konstantinos
Konstantopoulos, Zhan-You Wang, and Pu Wang.
By suppressing the expression of anterior
pharynx-defective-1a and -1ß and inhibiting the
aggregation of ß-amyloid protein, magnesium ions
inhibit the cognitive decline of amyloid precursor
protein/presenilin 1 transgenic mice.
FASEB J. December 2015 29:5044-5058;
doi:10.1096/fj.15-275578
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