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New articles from Prof. Weihong Song, our Associate Editor

Published on: 15 Sep 2021 Viewed: 426

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles from Prof. Weihong Song, our Associate Editor.

Title: Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice
Authors: Jun Wang, Bin-Lu Sun, Yang Xiang, Ding-Yuan Tian, Chi Zhu, Wei-Wei Li, Yu-Hui Liu, Xian-Le Bu, Lin-Lin Shen, Wang-Sheng Jin, Zhen Wang, Gui-Hua Zeng, Wei Xu, Li-Yong Chen, Xiao-Wei Chen, Zhian Hu, Zhi-Ming Zhu, Weihong Song, Hua-Dong Zhou, Jin-Tai Yu, Yan-Jiang Wang
Type: Article from Translational Psychiatry
Alzheimer’s disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.
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Title: Inhibition of cystathionine β-synthase promotes apoptosis and reduces cell proliferation in chronic myeloid leukemia
Authors: Dan Wang, Huan Yang, Yun Zhang, Rong Hu, Dongjie Hu, Qunxian Wang, Yannan Liu, Mingjing Liu, Zijun Meng, Weihui Zhou, Weihong Song
Type: Article of Signal Transduction and Targeted Therapy
Increased endogenous hydrogen sulfide (H2S) level by cystathionine β-synthase (CBS) has been shown to closely relate tumorigenesis. H2S promotes angiogenesis, stimulates bioenergy metabolism and inhibits selective phosphatases. However, the role of CBS and H2S in chronic myeloid leukemia (CML) remains elusive. In this study, we found that CBS and H2S levels were increased in the bone marrow mononuclear cells of pediatric CML patients, as well as in the CML-derived K562 cells and CBS expression levels were correlated with different disease phases. Inhibition of CBS reduced the proliferation of the CML primary bone marrow mononuclear cells and induced growth inhibition, apoptosis, cell cycle arrest, and migration suppression in K562 cells and tumor xenografts. The knockdown of CBS expression by shRNA and inhibiting CBS activity by AOAA decreased the endogenous H2S levels, promoted mitochondrial-related apoptosis and inhibited the NF-κB-mediated gene expression. Our study suggests that inhibition of CBS induces cell apoptosis, as well as limits cell proliferation and migration, a potential target for the treatment of chronic myeloid leukemia.
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Title: Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice
Authors: Hong Zheng, Pengtao Xu, Qiaoying Jiang, Qingqing Xu, Yafei Zheng, Junjie Yan, Hui Ji, Jie Ning, Xi Zhang, Chen Li, Limin Zhang, Yuping Li, Xiaokun Li, Weihong Song, Hongchang Gao
Type: Research of Microbiome
Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism.
We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy.
Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.
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Title: Cell-type-specific memory consolidation driven by translational control
Authors: Qing Zhang, Isabel Bestard-Lorigados, Weihong Song
Type: Research Highlight of Signal Transduction and Targeted Therapy
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Title: NLRP3 inflammasome as a novel therapeutic target for Alzheimer’s disease
Authors: Yun Zhang, Zhifang Dong, Weihong Song
Type: Research Highlight of Signal Transduction and Targeted Therapy
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Title: Identification of Alzheimer’s disease–associated rare coding variants in the ECE2 gene
Authors: Xinxin Liao, Fang Cai, Zhanfang Sun, Yun Zhang, Juelu Wang, Bin Jiao, Jifeng Guo, Jinchen Li, Xixi Liu, Lina Guo, Yafang Zhou, Junling Wang, Xinxiang Yan, Hong Jiang, Kun Xia, Jiada Li, Beisha Tang, Lu Shen, Weihong Song
Type: Article of JCI Insight
Accumulation of amyloid β protein (Aβ) due to increased generation and/or impaired degradation plays an important role in Alzheimer’s disease (AD) pathogenesis. In this report, we describe the identification of rare coding mutations in the endothelin-converting enzyme 2 (ECE2) gene in 1 late-onset AD family, and additional case-control cohort analysis indicates ECE2 variants associated with the risk of developing AD. The 2 mutations (R186C and F751S) located in the peptidase domain in the ECE2 protein were found to severely impair the enzymatic activity of ECE2 in Aβ degradation. We further evaluated the effect of the R186C mutation in mutant APP–knockin mice. Overexpression of wild-type ECE2 in the hippocampus reduced amyloid load and plaque formation, and improved learning and memory deficits in the AD model mice. However, the effect was abolished by the R186C mutation in ECE2. Taken together, the results demonstrated that ECE2 peptidase mutations contribute to AD pathogenesis by impairing Aβ degradation, and overexpression of ECE2 alleviates AD phenotypes. This study indicates that ECE2 is a risk gene for AD development and pharmacological activation of ECE2 could be a promising strategy for AD treatment.
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