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Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease

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Chinese Journal of Traumatology 2024年第3期27卷 125-133页

作者： Yan Zhao Yuan-Guo Zhou Jiang-Fan Chen Department of Army Occupational Disease State Key Laboratory of TraumaBurns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical University.Chongqing400042China The molecular Neuropharmacology Laboratory and the Eye-Brain Research Center The State Key Laboratory of OphthalmologyOptometry and Vision ScienceWenzhou Medical UniversityWenzhou325035Zhejiang ProvinceChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou325035Zhejiang ProvinceChina

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A *** adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)*** approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving *** this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive *** further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of ***,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease ***,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

关键词： Receptor,Adenosine A2A Adenosine A2 receptor antagonists Parkinson's disease Brain injuries,traumatic

Fibrinogen triggered signaling pathways modify stem cell behavior in central nervous system disease

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Neural Regeneration Research 2021年第6期16卷 1196-1197页

作者： Jia-Di Lin Yu-Hsuan Chu Suvra Nath Christian Schachtrup Institute of Anatomy and Cell Biology Faculty of MedicineUniversity of FreiburgFreiburgGermany Faculty of Biology University of FreiburgFreiburgGermany Center for Basics in neuromodulation(NeuroModulBasics) Faculty of MedicineUniversity of FreiburgFreiburgGermany

Neural stem/precursor cells(NSPCs)hold great promise in improving central nervous system(CNS)repair,either by triggering endogenous NSPC sources of the CNS or by transplantation of *** molecular mechanisms of NSPC survival and integration as well as their cell fate determination are still insufficiently understood,yet will be instrumental for harnessing these cells for brain *** our recent Nature Communications manuscript entitled“Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling”(Pous et al.,2020),we advanced towards understanding how CNS disease alters the brain subventricular zone(SVZ)stem cell niche environment by the disease-triggered deposition of blood-derived factors and how these factors regulate NSPC fate and brain repair.

关键词： Fibrinogen system stem

The roles of microglia in viral encephalitis:from sensome to therapeutic targeting

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Cellular & molecular Immunology 2021年第2期18卷 250-258页

作者： Chintan Chhatbar Marco Prinz Institute of Neuropathology Medical FacultyUniversity of FreiburgFreiburgGermany Center for Basics in neuromodulation(NeuroModulBasics) Faculty of MedicineUniversity of FreiburgFreiburgGermany Signalling Research Centres BIOSS and CIBSS University of FreiburgFreiburgGermany

Viral encephalitis is a devastating disease with high mortality,and survivors often suffer from severe neurological *** are innate immune cells of the central nervous system(CNS)parenchyma whose turnover is reliant on local *** express a diverse range of proteins,which allows them to continuously sense the environment and quickly react to *** inflammatory conditions such as CNS viral infection,microglia promote innate and adaptive immune responses to protect the ***,during viral infection,a dysregulated microglia-T-cell interplay may result in altered phagocytosis of neuronal synapses by microglia that causes neurocognitive *** this review,we summarize the current knowledge on the role of microglia in viral encephalitis,propose questions to be answered in the future and suggest possible therapeutic targets.

关键词： microglial activation viral encephalitis neurocognitive issues purinergic signaling PRR signaling

Rapid and specific detection of norepinephrine via a “hunting-shooting” strategy

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Science China Chemistry 2023年第4期66卷 923-925页

作者： Qi-Wei Zhang Yang Tian Shanghai Key Laboratory of Green Chemistry and Chemical Processes Department of ChemistrySchool of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

Neurotransmitters are important endogenous chemicals in the central and sympathetic nervous system of organisms,which play an important role in maintaining physiological processes,such as the signaling,neuromodulation... 详细信息

关键词： metabolism endogenous sympathetic

Boosting corticospinal system synaptic plasticity to recover motor functions

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Neural Regeneration Research 2023年第10期18卷 2182-2183页

作者： Weiguo Song John H.Martin Feinstein Institutes for Medical Research ManhassetNYUSA Department of molecular Cellularand Biomedical SciencesCenter for Discovery and Innovation Neuroscience Program Graduate Center of the City University of New YorkNew YorkNYUSA

An importa nt strategy to promote voluntary movements after motor system injury is to strengthen the connections between the motor cortex and muscles by taking advantage of the plasticity of the corticospinal motor *** neuromodulation approaches are directed to activate the spinal cord and peripheral axons to strengthen muscle *** discuss in this perspective that,the cortex and spinal cord should be ta rgeted together to enhance cortex-to-musclefunction(Amer and Martin,2022).

关键词： plasticity system activation

Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy

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Chinese Medical Journal 2021年第15期134卷 1845-1854页

作者： Ning Chen Jian-Guo Zhang Chun-Lei Han Fan-Gang Meng Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Beijing Key Laboratory of neuromodulation Beijing Municipal Science and Technology CommissionBeijing 100070China ieijing Neurosurgical Institute Capital Medical UniversityBeijing 100070China Chinese Institute for Brain Research Beijing 102206China

Background:Deep brain stimulation(DBS)has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain *** study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular ***:We established a macaque model of mesial temporal lobe epilepsy(mTLE),and continuous high-frequency hippocampus DBS(hip-DBS)was applied for 3 *** effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics ***,the microarray results were validated using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot ***:The results showed that chronic hip-DBS modulated the hippocampal gene *** identified 4119 differentially expressed genes and assigned these genes to 16 model *** test of cluster analysis showed that profiles 5,3,and 2 were the predominant expression ***,profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction *** dysregulated genes(Arhgap5,Colla2,Itgbl^Pik3rl,Lama4,Fnl,Col3al,Itga9,and Shc4)and three genes(Colla2,Itgbl,and Flna)in these two pathways were further validated by qRT-PCR and Western blot analyses,respectively,which showed a ***:Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene *** from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

关键词： Deep brain stimulation Gene expression profile Hippocampus Temporal lobe epilepsy

Vagal-mAChR4 signaling promotes Friend virus complex(FV)-induced acute erythroleukemia

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Virologica Sinica 2023年第3期38卷 429-439页

作者： Shuting Song Zhekai Lin Caiqi Zhao Jing Wen Jie Chen Shitao Xie Huaxin Qi Jianhua Wang Xiao Su Unit of Respiratory Infection and Immunity Institute Pasteur of ShanghaiChinese Academy of SciencesShanghai200031China CAS Key Laboratory of molecular Virology and Immunology Institute Pasteur of ShanghaiChinese Academy of SciencesShanghai200031China University of Chinese Academy of Sciences Beijing101408China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou510530China Shanghai Key Laboratory of Lung Inflammation and Injury Shanghai200031China

Erythroleukemia belongs to acute myeloid leukemia(AML)type 6(M6),and treatment remains difficult due to the poor prognosis of the *** virus(FV)is a complex of two viruses:Friend murine leukemia virus(F-MuLV)strain along with a defective spleen focus-forming virus(SFFV),which can induce acute eryth-roleukemia in *** have previously reported that activation of vagalα7 nicotinic acetylcholine receptor(nAChR)signaling promotes HIV-1 *** vagal muscarinic signaling mediates FV-induced erythroleukemia and the underlying mechanisms remain *** this study,sham and vagotomized mice were intraperitoneally injected with *** infection caused anemia in sham mice,and vagotomy reversed this *** infection increased erythroblasts ProE,EryA,and EryB cells in the spleen,and these changes were blocked by *** bone marrow,FV infection reduced EryC cells in sham mice,an effect that was coun-teracted by *** infection increased choline acetyltransferase(ChAT)expression in splenic CD4^(+)and CD8þT cells,and this change was reversed by ***,the increase of EryA and EryB cells in spleen of FV-infected wild-type mice was reversed after deletion of ChAT in CD4^(+)T *** bone marrow,FV infection reduced EryB and EryC cells in sham mice,whereas lack of ChAT in CD4^(+)T cells did not affect this *** of muscarinic acetylcholine receptor 4(mAChR4)by clozapine N-oxide(CNO)significantly increased EryB in the spleen but decreased the EryC cell population in the bone marrow of FV-infected ***,vagal-mAChR4 signaling in the spleen and bone marrow synergistically promotes the pathogenesis of acute *** uncover an unrecognized mechanism of neuromodulation in erythroleukemia.

关键词： Vagus nerve Friend virus(FV) Acute erythroleukemia Erythroblast Choline acetyltransferase(ChAT)

ADAR1 averts fatal type I interferon induction by ZBP1

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四川生理科学杂志 2022年第7期44卷 1307-1307页

作者： Huipeng Jiao Institute for Genetics University of Cologne Cologne Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) University of Cologne Cologne Germany Center for molecular Medicine (CMMC) University of Cologne Cologne Germany In Vivo Research Facility Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany Institute for Pathology Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany Institute of Surgical Pathology Faculty of Medicine Medical Center–University of Freiburg Freiburg Germany Institute of Neuropathology Medical Faculty University of Freiburg Freiburg Germany Centre for neuromodulation (NeuroModBasics) University of Freiburg Freiburg Germany Signalling Research Centres BIOSS and CIBSS University of Freiburg Freiburg Germany Bioinformatics and Biostatistics STP London UK Retroviral Immunology The Francis Crick Institute London UK Department of Infectious Disease Imperial College London London UK

Mutations of the ADAR1 gene encoding an RNA deaminase cause severe diseases associated with chronic activation of type I interferon(IFN)responses,including Aicardi-Goutières syndrome and bilateral striatal *** IFN-inducible p150 isoform of ADAR1 contains a Zαdomain that recognizes RNA with an alternative left-handed double-helix structure,termed Z-RNA4,*** ADAR1 mutations in the Zαdomain cause type I IFN-mediated pathologies in humans2,3 and mice6-8;however,it remains unclear how the interaction of ADAR1 with Z-RNA prevents IFN *** we show that Z-DNA-binding protein 1(ZBP1),the only other protein in mammals known to harbour Zαdomains9,promotes type I IFN activation and fatal pathology in mice with impaired ADAR1 ***1 deficiency or mutation of its Zαdomains reduced the expression of IFN-stimulated genes and largely prevented early postnatal lethality in mice with hemizygous expression of ADAR1 with mutated Zαdomain(Adar1mZα/-mice).Adar1mZα/-mice showed upregulation and impaired editing of endogenous retroelement-derived complementary RNA reads,which represent a likely source of Z-RNAs activating ZBP1.

关键词： ADAR1 impaired endogenous

Rosamine-based fluorescent chemodosimeter for hydrogen sulfide and its bioimaging in live cells

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Rosamine-based fluorescent chemodosimeter for hydrogen sulfi...