Se-Methylselenocysteine (SMC) Improves Cognitive Deficits by Attenuating Synaptic and Metabolic Abnormalities in Alzheimer’s Mice Model: A Proteomic Study

Abstract

Se-methylselenocysteine (SMC) is a major selenocompound in selenium (Se) enriched plants and has been found to ameliorate neuropathology and cognitive deficits in triple-transgenic mice model of Alzheimer’s disease (3 × Tg-AD mice). To explore the underlying molecular mechanisms, the present study is designed to elucidate the protein changes in the cortex of SMC-treated 3 × Tg-AD mice. After SMC supplementation, proteomic analysis revealed that 181, 271, and 41 proteins were identified as differentially expressed proteins (DEPs) between 3 × Tg-AD mice vs wild type (AD/WT group), SMC-treated AD mice vs AD (AD + SMC/AD), and AD + SMC/WT group, respectively. Among these, 138 proteins in the diseased group were reversed by SMC treatment. The DEPs in AD/WT group and AD + SMC/AD group were mainly related to metabolism, synapses, and antioxidant proteins, while their levels were decreased in AD mice but up-regulated after treating with SMC. In addition, we found reduced ATP levels and destroyed synaptic structures in the AD mice brains, which were significantly ameliorated upon SMC treatment. Our study suggests that energy metabolism disorders, abnormal amino acid metabolism, synaptic dysfunction, and oxidative stress may be the key pathogenic phenomena of AD. SMC reversed the expression of proteins associated with them, which might be the main mechanism of its intervention in AD.

iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery

“…However, it needs to be pointed out that in patients with HD, AD, PD, and ALS, mitochondrial dysfunction and energy metabolism are decreased. Proteins related to oxidative phosphorylation and ETC are usually downregulated. − On the contrary, in the cerebral cortex of VPA rats in this study, as mentioned above, the expression of these DEPs related to metabolic pathways was upregulated.…”

Investigating the Neurotoxic Impacts of Arsenic and the Neuroprotective Effects of Dictyophora Polysaccharide Using SWATH-MS-Based Proteomics

“…DEPs were analyzed by GO (gene ontology) annotation, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, and protein−protein interaction (PPI) networks. GO annotations included the biological process (BP) and cellular component (CC) [ 35 ]. Hub genes were screened by cytohubba software.…”

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

“…There is increasing evidence that several Se compounds have therapeutic potential for AD. SMC is mainly found in seleno-containing plants, and studies have shown that SMC regulates oxidative stress and synaptic function in the brain, thereby improving cognitive impairment in AD mice [ 14 , 18 ]. SeM, the main chemical form of Se consumed by humans, alleviates cognitive impairment in AD mice by reducing Aβ deposition and tau hyperphosphorylation [ 17 , 21 ].…”

“…SeNa was initially found to affect tau hyperphosphorylation by regulating the activity of protein phosphatase 2 (PP2A) [ 11 ]. The activation of autophagic flux mediated by SeM was found to promote the clearance of Aβ and tau [ 16 , 17 ], and SMC has been shown to have a positive effect on synaptic abnormalities in AD [ 18 ]. Although multiple pathways have been implicated in the amelioration of AD pathologies by Se, the differences and similarities in molecular mechanisms among Se compounds remain to be elucidated.…”