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Copper homeostasis and neurodegenerative diseases

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Neural Regeneration research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang international research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

Prefrontocortical Astrocytes Regulate Dominance Hierarchy in Male Mice

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Neuroscience Bulletin 2024年第3期40卷 415-417页

作者： Yong Tang Hai-Yan Yin Peter Illes School of Acupuncture and Tuina Chengdu University of Traditional Chinese MedicineChengdu 610075China international joint research center on purinergic signaling Chengdu University of Traditional Chinese MedicineChengdu 610075China Rudolf Boehm Institute for Pharmacology and Toxicology University of Leipzig04107 LeipzigGermany

Social hierarchy is a general self-organizational scheme in animal societies in which each member achieves a certain status of domination or subordination when getting access to resources,with profound consequences for survival,health,reproductive success,and multiple behaviors[1,2].The prefrontal cortex(PFC)was recognized as a central regulator of neuronal circuits determining the formation of social hierarchy;brain areas upstream of the PFC convey information about social status,and downstream brain regions execute dominance behavior[3].Social deficits have been suggested to be due to an elevation of excitatory/inhibitory(E/l)balance within the mouse dorsomedial(dm)PFC[4].A compensatory increase of inhibitory cell excitability partially rescued social deficits caused by such a disturbance of E/l balance.

关键词： consequences hierarchy determining

Surveilling microglia dampens neuronal activity:operation of a purinergically mediated negative feedback mechanism

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1413-1415页

作者： Peter Illes Alexei Verkhratsky Yong Tang Rudolf Boehm Institute for Pharmacology and Toxicology University of LeipzigLeipzigGermany School of Acupuncture and Tuina Chengdu University of Traditional Chinese MedicineChengduChina international Collaborative center on Big Science Plan for purinergic signaling Chengdu University of Traditional Chinese MedicineChengduChina Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK

The recent paper published in Nature by Badimon et *** that neuronal activity via the stimulation of surveilling microglia feeds back to inhibit neuronal networks.1 This effect is mediated by the release of ATP from the terminals of excitatory neurons;subsequently,ATP is degraded to adenosine by microglial enzymes,imposing an inhibitory,A1 receptor(R)-mediated control on the hyperactive neurons themselves.

关键词： mediated stimulation operation

Interaction of brassinosteroid and cytokinin promotes ovule initiation and increases seed number per silique in Arabidopsis

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Journal of Integrative Plant Biology 2022年第3期64卷 702-716页

作者： Song-Hao Zu Yu-Tong Jiang Jin-Hui Chang Yan-Jie Zhang Hong-Wei Xue Wen-Hui Lin School of Life Sciences and Biotechnology The Joint International Research Laboratory of Metabolic and Developmental SciencesJoint Center for Single Cell BiologyShanghai Jiao Tong UniversityShanghai 200240China School of Agriculture and Biology Joint Center for Single Cell BiologyShanghai Jiao Tong UniversityShanghai 200240China

Ovule initiation is a key step that strongly influences ovule number and seed ***,mutants with enhanced brassinosteroid(BR)and cytokinin(CK)signaling produce more ovules and have a higher seed number per silique(SNS)than wild-type ***,we crossed BR-and CKrelated mutants to test whether these phytohormones function together in ovule *** determined that simultaneously enhancing BR and CK contents led to higher ovule and seed numbers than enhancing BR or CK separately,and BR and CK enhanced each ***,the BR-response transcription factor BZR1 directly interacted with the CK-response transcription factor ARABIDOPSIS RESPONSE REGULATOR1(ARR1).Treatments with BR or BR plus CK strengthened this interaction and subsequent ARR1 targeting and induction of downstream genes to promote ovule *** CK signaling partially rescued the reduced SNS phenotype of BR-deficient/insensitive mutants whereas enhanced BR signaling failed to rescue the low SNS of CK-deficient mutants,suggesting that BR regulates ovule initiation and SNS through CK-mediated and-independent *** study thus reveals that interaction between BR and CK promotes ovule initiation and increases seed number,providing important clues for increasing the seed yield of dicot crops.

关键词： brassinosteroid cytokinin ovule initiation protein interaction seed number per silique

Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks

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Chinese Journal of Natural Medicines 2016年第4期14卷 241-254页

作者： LIU Hai-Xin WANG Yu LU Qing YANG Ming-Zhu FAN Guan-Wei KARAS Richard H GAO Xiu-Mei ZHU Yan Tianjin State Key Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese Medicine research and Development center of Traditional Chinese Medicine Tianjin International Joint Academy of Biotechnology & Medicine Molecular Cardiology research Institute Tufts Medical Center

Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERa and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERa and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERa, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERa and ERβ may be critical in the balance of pro- or anti-angiogenesis process.

关键词： Phytoestrogen Selective estrogen receptor modifies (SERMs) ERa ERβ Bidirectional regulation of angiogenesis IPA

OsPHR2-mediated recruitment of Pseudomonadaceae enhances rice phosphorus uptake

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Plant Communications 2024年第8期5卷 137-146页

作者： Jianping Liu Weifeng Xu Qian Zhang Wencheng Liao Liang Li Shu Chen Jinyong Yang Zhengrui Wang Feiyun Xu center for Plant Water-use and Nutrition Regulation and College of JunCao Science and Ecology Joint International Research Laboratory of Water and Nutrient in CropFujian Agriculture and Forestry UniversityFuzhou 350002China

Plants can shape their root microbiome to promote growth and nutrient *** STARVATION RESPONSE 2(OsPHR2)is a central regulator of phosphate signaling in rice,but whether OsPHR2 can shape the root microbiome to promote phosphorus uptake is ***,we investigate the role of OsPHR2 in recruiting microbiota for phosphorus uptake using high-throughput sequencing and metabolite ***2-overexpressing(OsPHR2 OE)rice showed 69.8%greater shoot P uptake in natural soil compared with sterilized soil under high-phosphorus(HP)conditions,but there was only a 54.8%increase in the wildtype(WT).The abundance of the family Pseudomonadaceae was significantly enriched in OsPHR2 OE roots relative to those of WT *** with the WT,OsPHR2 OE rice had a relatively higher abundance of succinic acid and methylmalonic acid,which could stimulate the growth of Pseudomonas sp.(P6).After inoculation with P6,phosphorus uptake in WT and OsPHR2 OE rice was higher than that in uninoculated rice under low-phosphorus(LP)*** together,our results suggest that OsPHR2 can increase phosphorus use in rice through root exudate-mediated recruitment of *** finding reveals a cooperative contribution of the OsPHR2-modulated root microbiome,which is important for improving phosphorus use in agriculture.

关键词： OsPHR2 rice organic acid phosphorus Pseudomonadaceae

Activated STING: an ion channel to trigger non-interferon-related functions

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5143-5145页

作者： Zhengyu Gao Bin Wang Long Zhang international Biomed-X research center Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouChina MOE Laboratory of Biosystems Homeostasis and Protection and Innovation center for Cell signaling Network Life Sciences InstituteZhejiang University310058HangzhouChina

Recently,a study published in Science by Liu et al.1 presented compelling evidence demonstrating that upon translocation to the Golgi apparatus,STING(Stimulator of Interferon Genes)serves as a direct mediator for proton release into the cytosol,thereby instigating non-canonical LC3B(light-chain 3B)lipidation and NLRP3(NOD-like receptor family pyrin domain–containing 3)inflammasome activation(Fig.1).This study offers a new perspective on the involvement of the cGAS-STING pathway in non-interferon-related functions.

关键词： functions thereby apparatus

Application and prospects of proteomic technology in inflammation:a review

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Food Science and Human Wellness 2024年第5期13卷 2373-2385页

作者： Senye Wang Yanhai Chu Jiajia Yuan Yiqi Li Zhenhua Liu Xiaoyu Chen Wenyi Kang National R&D center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Functional Food Engineering Technology research center Kaifeng 475004China joint international research Laboratory of Food&Medicine Resource Function Kaifeng 475004China College of Agriculture Henan UniversityKaifeng 475004China

Proteomics is a new technology that has been widely applied in the field of life and health *** effectively addresses issues related to the impact of dietary structure on organs,tissues,and cells,as well as the changes in proteins in various organs,tissues,and cells under disease *** differential proteins identified through proteomics can serve as disease biomarkers and target proteins affecting health and can be used for disease diagnosis and health *** this paper,the application of proteomics in the field of infl ammation in recent years was summarized,especially in the therapeutic target and mechanism of action,which opens up a new way for more effective prevention,diagnosis,and treatment of inflammation,and provides medical protection for human life and health.

关键词： Proteomics technology Inflammation Biomarkers Potential target signaling pathway

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical research center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine