Article
Biochemistry & Molecular Biology
Tan Yan, Wang Ya-Lei, Peng Tian-Tian, Zhang Ya-Li, Zhang Hua-Wei, Chen Wei-Hang, Yang Ke, Zhang Jia-Ni, Wang Xu, Wei Peng, Liu Zhao-Heng, Yang Kai-Yu, Liu Tong-Hua, Hua Qian
Summary: This study aimed to investigate the age and gender differences in APP V717I transgenic mice during the progression of Alzheimer's disease (AD). The results showed that female mice exhibited significant anxiety at 6 months of age, while male mice only showed anxiety at 10 months. Both genders displayed cognitive impairments at 10 months but not at 6 months. These findings suggest that there are distinct age and gender differences in AD progression, and the APP V717I mouse model could serve as a valuable tool for AD research and precision medicine.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Neurosciences
Stephen M. Day, Stephen C. Gironda, Caitlin W. Clarke, J. Andy Snipes, Noelle I. Nicol, Hana Kamran, Warner Vaughan, Jeffrey L. Weiner, Shannon L. Macauley
Summary: This study used a moderate drinking paradigm to investigate the effects of chronic ethanol exposure on Alzheimer's disease-related pathology, behavior, and metabolism. Ethanol-exposed mice showed increased brain atrophy, amyloid plaques, and shifts in plaque size distribution. They also exhibited deficits in self-care, increased locomotor activity, altered feeding behavior, and changes in glucose homeostasis. These findings suggest that ethanol may increase A beta deposition by disrupting metabolism and the brain's E/I balance, ultimately leading to AD-related phenotypes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Catalina Anca Cucos, Elena Milanesi, Maria Dobre, Ioana Andreea Musat, Gina Manda, Antonio Cuadrado
Summary: This study aimed to identify inflammatory and redox dysregulations in the context of AD-specific neuronal cell death and DNA damage using the APP(V717I)xTAU(P301L) (AT) mouse model. By evaluating gene expression in the hippocampus and blood of AT mice, potential candidate biomarkers for preclinical drug development were identified. These findings may be valuable in translating research results into clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Diana M. Bessa de Sousa, Ariane Benedetti, Barbara Altendorfer, Heike Mrowetz, Michael S. Unger, Katharina Schallmoser, Ludwig Aigner, Kathrin Maria Kniewallner
Summary: In Alzheimer's disease, dysfunctional platelets may contribute to amyloid beta deposition. Platelet depletion in APP-PS1 transgenic mice led to an increase in amyloid plaque size distribution and neuritic dystrophy in the hippocampus of female mice. It was found that platelet-depleted females had lower amounts of amyloid beta cargo and increased overlap between astrocytic processes and amyloid plaques. These findings suggest that platelets might limit plaque growth and reduce plaque-related neuritic dystrophy at advanced stages of amyloid plaque pathology in APP-PS1 female mice.
Article
Neurosciences
Wenqiang Quan, Qinghua Luo, Wenlin Hao, Inge Tomic, Tomomi Furihata, Walter Schulz-Schaffer, Michael D. Menger, Klaus Fassbender, Yang Liu
Summary: Conditional deletion of one allele of the myd88 gene specifically in microglia of APP/PS1-transgenic mice reduced cerebral amyloid beta load, improved cognitive function, decreased microglial numbers and inhibited inflammatory gene transcription. Haploinsufficiency of MyD88 in microglia at a late disease stage attenuated pro-inflammatory activation and amyloid pathology, prevented microvasculature impairment, and protected LRP1-mediated A beta clearance, ultimately improving neuronal function in AD mice.
Article
Pharmacology & Pharmacy
Laura Vidal-Palencia, Carla Ramon-Duaso, Jose Antonio Gonzalez-Parra, Arnau Busquets-Garcia
Summary: This study aims to expand our knowledge of the ECS status in a presymptomatic period by using the AD mouse model APP/PS1 mice. The research found that at 3 months of age, the expression of ECS in different brain regions showed differences depending on sex, indicating ECS alterations in APP/PS1 mice at the presymptomatic stage.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, Juan Jose Fernandez-Valenzuela, Vanessa De Castro, Marina Mejias-Ortega, Angela Gomez-Arboledas, Sebastian Jimenez, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Ines Moreno-Gonzalez, David Baglietto-Vargas, Marisa Vizuete, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez
Summary: Alzheimer's disease is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. Synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Yanxing Chen, Shuai Zhao, Ziqi Fan, Zheyu Li, Yueli Zhu, Ting Shen, Kaicheng Li, Yaping Yan, Jun Tian, Zhirong Liu, Baorong Zhang
Summary: The study uncovered a crosstalk between amyloid and NP tau pathology, where Aβ plaques promoted the aggregation of NP tau, and metformin enhanced microglial autophagy capability to promote the phagocytosis of pathological Aβ and tau proteins, reducing Aβ deposits and limiting the spreading of NP tau pathology.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Medicine, Research & Experimental
Lingyu She, Li Xiong, Liwei Li, Jing Zhang, Jinfeng Sun, Haibin Wu, Juan Ren, Wei Wang, Xia Zhao, Guang Liang
Summary: Alzheimer's disease is a major public health problem with no effective treatment. This study found that the main bioactive component in ginseng, Rk3, has strong antioxidant effects and can improve the progression of Alzheimer's disease. These findings suggest that Rk3 may be a new strategy for the treatment of Alzheimer's disease.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Public, Environmental & Occupational Health
Mikaela Bloomberg, Aline Dugravot, Julien Dumurgier, Mika Kivimaki, Aurore Fayosse, Andrew Steptoe, Annie Britton, Archana Singh-Manoux, Severine Sabia
Summary: The study found that education level plays a role in influencing sex differences in cognitive aging. Women generally performed better in memory tasks, while men had faster memory decline. Sex differences in fluency varied by birth cohort and education level. The findings suggest that reducing educational disparities between sexes could help alleviate sex differences in dementia risk and cognitive decline in the future.
LANCET PUBLIC HEALTH
(2021)
Article
Immunology
Jing Sun, Yuhe Zhang, Yu Kong, Tao Ye, Qingxia Yu, Senthil Kumaran Satyanarayanan, Kuan-Pin Su, Jiaming Liu
Summary: Alterations in gut microbiota may impact the development of Alzheimer's disease through the production of microbiota-derived metabolites. In this study, it was found that indoles produced by bacteria in the gut regulated neuroinflammation in AD by activating the AhR pathway, reducing inflammatory response, and potentially offering a new approach for AD treatment.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Immunology
Othman Othman, Hayley Marshall, Mitchell Masterson, Poppy Winlow, Graham Gibson, Yuchun Ding, Marie-Christine Pardon
Summary: This study found that T beta 4 can alleviate the inflammatory response caused by lipopolysaccharide (LPS) in the gut, and reduce sickness symptoms in a mouse model of Alzheimer's disease. The treatment prevented amyloid burden in Alzheimer's mice and induced reactive microgliosis in aging wildtype mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Food Science & Technology
Chuan Qin, Shaoqin Hu, Shuangxi Zhang, Daina Zhao, Yongyao Wang, Hua Li, Yunhua Peng, Le Shi, Xiaohong Xu, Changhe Wang, Jiankang Liu, Ying Cheng, Jiangang Long
Summary: The study found that HT-ac significantly improved cognitive function in AD mice by ameliorating neuronal apoptosis and decreasing inflammatory cytokine levels in water maze tests.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Neurosciences
Zhang Chenfei, Yu Haizhen, Xia Jie, Zhao Na, Xu Bo
Summary: Exercise can improve learning and memory impairments in AD mice by reducing SUMO1 modification in the hippocampus, but has no significant effect on SUMO2/3 modification.
NEUROSCIENCE LETTERS
(2022)
Article
Neurosciences
Gael Barthet, Ana Moreira-de-Sa, Pei Zhang, Jorge Castanheira, Adam Gorlewicz, Christophe Mulle
Summary: Kainate receptors (KARs) play a role in regulating neuronal networks and have been implicated in epilepsy. This study investigates the role of KARs in Alzheimer's disease (AD) and finds that the synaptic expression and function of KARs are impaired in mouse models of AD. The study also suggests that the protein APP stabilizes KARs at synapses through a transsynaptic mechanism, and this interaction is regulated by the c-secretase proteolytic activity of presenilin.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Xin Zhao, Runfeng Li, Yang Zhou, Mengjie Xiao, Chunlong Ma, Zhongjin Yang, Shaogao Zeng, Qiuling Du, Chunguang Yang, Haiming Jiang, Yanmei Hu, Kefeng Wang, Chris Ka Pun Mok, Ping Sun, Jianghong Dong, Wei Cui, Jun Wang, Yaoquan Tu, Zifeng Yang, Wenhui Hu
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Geriatrics & Gerontology
Ping Sun, Gabriela Ortega, Yan Tan, Qian Hua, Peter F. Riederer, Juergen Deckert, Angelika G. Schmitt-Boehrer
FRONTIERS IN AGING NEUROSCIENCE
(2018)
Article
Biochemistry & Molecular Biology
Ping Sun, Wei Zhou, Hu Yue, Cheng Zhang, Yitao Ou, Zhongjin Yang, Wenhui Hu
ACS CHEMICAL NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Wenmin Deng, Zhongjin Yang, Hu Yue, Yitao Ou, Wenhui Hu, Ping Sun
FREE RADICAL BIOLOGY AND MEDICINE
(2020)
Article
Chemistry, Medicinal
Yitao Ou, Ping Sun, Nannan Wu, Hao Chen, Dan Wu, Wenhui Hu, Zhongjin Yang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Chemistry, Medicinal
Hao Chen, Xiuhui Chen, Ping Sun, Dan Wu, Hu Yue, Jintao Pan, Xinxuan Li, Cheng Zhang, Xinyi Wu, Lei Hua, Wenhui Hu, Zhongjin Yang
Summary: Compound 8c was found to significantly inhibit NLRP3-mediated IL-1 beta release and alleviate peritoneal inflammation in a mouse model. It is a promising lead compound for further chemical development as a NLRP3 inhibitor with anti-inflammation effects.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Cheng Zhang, Hu Yue, Ping Sun, Lei Hua, Shuli Liang, Yitao Ou, Dan Wu, Xinyi Wu, Hao Chen, Ying Hao, Wenhui Hu, Zhongjin Yang
Summary: The study identified a novel and potent class of NLRP3 inflammasome inhibitors, with lead compound 40 showing improved inhibitory potency and therapeutic effects in sepsis and colitis treatment. The compound was found to inhibit NLRP3 inflammasome activation by suppressing ROS production.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Hu Yue, Zhongjin Yang, Yitao Ou, Shuli Liang, Wenmin Deng, Hao Chen, Cheng Zhang, Lei Hua, Wenhui Hu, Ping Sun
Summary: Tanshinones, derived from the roots of Salvia miltiorrhiza, are active ingredients widely used in traditional medicine for treating inflammatory diseases. This study identified 15 tanshinones that suppress the activation of NLRP3 inflammasome, with specific tanshinones showing potential mitochondrial protection via promoting autophagy and the AMP-activated protein kinase pathway. The findings suggest that tanshinones, particularly dihydrotanshinone I, may offer a pharmacological mechanism for effectively treating inflammatory diseases like septic and gouty inflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Xiaotao Huang, Ping Sun, Yuyan Qin, Xiao-juan Wang, Mengyi Wang, Yongtong Lin, Ruiqing Zhou, Wenhui Hu, Qifa Liu, Xiyong Yu, Aiping Qin
Summary: This study demonstrated that treatment with disulfiram (DSF) effectively attenuated pulmonary injury and improved survival in a murine CMV pneumonia model. The anti-inflammatory effects of DSF may be attributed to its regulation of NF-KB signaling and NLRP3 inflammasome activation. DSF has potential as a therapy for human CMV pneumonia.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Neurosciences
Ying Hao, Yitao Ou, Cheng Zhang, Hao Chen, Hu Yue, Zhongjin Yang, Xiaofen Zhong, Wenhui Hu, Ping Sun
Summary: More than 30% of epilepsy patients are unresponsive to current drugs, necessitating the development of new candidate drugs. Ferroptosis plays a crucial role in epileptic seizures and has potential as a drug target. Seratrodast, a market drug for thromboxane A2 receptor antagonist, has been discovered as a new ferroptosis inhibitor with potential therapeutic effects on seizures.
Article
Biochemistry & Molecular Biology
Yanhong Chen, Xiuhui Chen, Shuli Liang, Yitao Ou, Geng Lin, Lei Hua, Xinyi Wu, Yinghua Zhou, Zhuorong Liu, Haowei Cai, Zhongjin Yang, Wenhui Hu, Ping Sun
Summary: Psoriasis is a chronic autoimmune skin disease associated with inflammation, and the antimicrobial agent chlorquinaldol (CQD) has been found to inhibit the activation of inflammasomes and reduce the severity of psoriatic response.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Pharmacology & Pharmacy
Shuli Liang, Zhongjin Yang, Lei Hua, Yanhong Chen, Yinghua Zhou, Yitao Ou, Xiuhui Chen, Hu Yue, Xiangyu Yang, Xinyi Wu, Wenhui Hu, Ping Sun
Summary: In this study, ciclopirox (CPX) was found to inhibit the activation of NLRP3 inflammasome by upregulating the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. CPX also reduced mitochondrial reactive oxygen species production, increased mitochondrial membrane potential, elevated mitochondrial biosynthesis, and up-regulated intracellular adenosine triphosphate level, leading to its anti-inflammatory effects. In addition, CPX showed therapeutic effects in a psoriasis mouse model.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiuhui Chen, Yanhong Chen, Yitao Ou, Wenjie Min, Shuli Liang, Lei Hua, Yinghua Zhou, Cheng Zhang, Peifeng Chen, Zhongjin Yang, Wenhui Hu, Ping Sun
Summary: The abnormal activation of NLRP3 inflammasome is important in the pathogenesis of psoriasis. Bortezomib, a marketed drug for treating multiple myeloma, specifically inhibits NLRP3 inflammasome activation and may be a potential therapeutic drug for psoriasis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Xinyi Wu, Ping Sun, Xiuhui Chen, Lei Hua, Haowei Cai, Zhuorong Liu, Cheng Zhang, Shuli Liang, Yanhong Chen, Dan Wu, Yitao Ou, Wenhui Hu, Zhongjin Yang
Summary: This study discovered an orally bioavailable proteasome inhibitor NIC-0102 that specifically inhibits NLRP3 inflammasome activation. It also demonstrated that NIC-0102 shows potent anti-inflammatory effects on an in vivo ulcerative colitis model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ping Sun, Hu Yue, Qi Xing, Wenmin Deng, Yitao Ou, Guangjin Pan, Xiaofen Zhong, Wenhui Hu
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)