Se-Methylselenocysteine Ameliorates Neuropathology and Cognitive Deficits by Attenuating Oxidative Stress and Metal Dyshomeostasis in Alzheimer Model Mice

Yongli Xie; Qiong Liu; Lin Zheng; BingTao Wang; Xiaogang Qu; Jiazuan Ni; Yan Zhang; Xiubo Du

doi:10.1002/mnfr.201800107

Se-Methylselenocysteine Ameliorates Neuropathology and Cognitive Deficits by Attenuating Oxidative Stress and Metal Dyshomeostasis in Alzheimer Model Mice

Mol Nutr Food Res. 2018 Jun;62(12):e1800107. doi: 10.1002/mnfr.201800107. Epub 2018 May 28.

Authors

Yongli Xie¹, Qiong Liu², Lin Zheng¹, BingTao Wang³, Xiaogang Qu⁴, Jiazuan Ni¹, Yan Zhang¹, Xiubo Du¹

Affiliations

¹ College of Life Sciences and Oceanography, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, P. R. China.
² Department of Marine Biology, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, 518060, P. R. China.
³ Shenzhen Entry-Exit Inspection and Quarantine Bureau, Futian Huanggang Port, Shenzhen, 518033, Guangdong Province, P. R. China.
⁴ State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

PMID: 29688618
DOI: 10.1002/mnfr.201800107

Abstract

Scope: Se-methylselenocysteine (SMC) is a major selenocompound in selenium (Se)-enriched plants. Se is vital for proper brain function, and Se-deficient is considered to be related with cognitive impairment and Alzheimer's disease (AD). The potential of SMC in intervening cognitive deficits and neuropathology of triple transgenic AD (3 × Tg-AD) mice is evaluated for the first time.

Methods and results: AD mice are treated with SMC (0.75 mg kg^-1 BW per day) in their drinking water for 10 months. Results reveal that SMC 1) reduces oxidative stress and neuro-inflammation; 2) modulates the distribution and levels of several metal ions; 3) decreases amyloid-β peptide (Aβ) generation by inhibiting the expression of its precursor protein APP and β-secretase (BACE1); and 4) attenuates tau hyperphosphorylation and neurofibrillary tangles (NFT) formation via promoting protein phosphatase 2A (PP2A) activity, thereby preserving synaptic proteins and neuron activities and finally improving spatial learning and memory deficits in AD model mice. The authors suggest that the inhibitory effect of SMC on MEK/ERK activation may play a critical role in intervening AD progression.

Conclusions: These results reveal that SMC is powerful in ameliorating AD-related neuropathology and cognitive deficits via modulating oxidative stress, metal homeostasis, and extracellular signal-regulated kinase (ERK) activation.

Keywords: Alzheimer's disease (AD); Aβ; Se-methylselenocysteine (SMC); extracellular signal-regulated kinase (ERK); metal homeostasis; tau.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / physiopathology*
Amyloid beta-Peptides / metabolism
Animals
Brain / drug effects*
Brain / metabolism
Brain / pathology
Cognitive Dysfunction / drug therapy*
Disease Models, Animal
Homeostasis / drug effects
MAP Kinase Signaling System / drug effects
Male
Metals / metabolism
Mice, Transgenic
Neurons / drug effects
Neurons / pathology
Oxidative Stress / drug effects
Phosphorylation / drug effects
Selenocysteine / analogs & derivatives*
Selenocysteine / pharmacology
Spatial Memory / drug effects
tau Proteins / metabolism

Substances

Amyloid beta-Peptides
Mapt protein, mouse
Metals
tau Proteins
Selenocysteine
selenomethylselenocysteine