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The pathogenesis of Parkinson’s disease and crosstalk with other diseases

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BIOCELL 2024年第8期48卷 1155-1179页

作者： TINGTING LIU DINGYOU GUO JIANSHE WEI institute for Brain sciences research School of Life SciencesHenan UniversityKaifeng475004China

In China,Parkinson’s disease(PD)is the second most prevalent central nervous system(CNS)degenerative illness affecting middle-aged and older *** disorders including resting tremor,bradykinesia,myotonia,postural instability,and gait instability are the predominant clinical *** two main types of PD are sporadic and familial,with sporadic PD being the more prevalent of the *** environment,genetics,mitochondrial dysfunction,oxidative stress,inflammation,protein aggregation and misfolding,loss of trophic factors,cell death,and gut microbiota may all have a role in the etiology of *** is inversely connected with other cancers and positively correlated with COVID-19,diabetes mellitus(DM),melanoma,and ischemic heart disease(IHD)*** disease progression,managing motor and non-motor symptoms,and avoiding and controlling dysfunction in the middle and later phases of the disease are the key areas of research and development for its ***,the development and progression of PD can be slowed down by using conventional pharmacology,natural items,and innovative *** article reviews the pathogenesis of PD,its correlations with other non-genetic diseases,and the research progress of drugs and technologies for alleviating PD.

关键词： Parkinson’s disease Mitochondrial dysfunction Oxidative stress Inflammation cancer Therapies

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

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Neural Regeneration research 2024年第6期19卷 1241-1248页

作者： Tingting Han Yuxiang Xu Lin Sun Makoto Hashimoto Jianshe Wei institute for Brain sciences research School of Life Sciences Henan University College of Chemistry and Molecular sciences Henan University Department of Basic Technology Tokyo Metropolitan Institute of Medical Science

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging; they have a great impact on the aging process and are the main risk factors for neurodegeneration. Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases. This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s chorea, and Parkinson’s disease. This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states. Therefore, inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

关键词： aging Alzheimer's disease cytokines Huntington's disease microglia neurodegenerative diseases neuroinflammation neuroprotection neurotoxicity Parkinson's disease

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun cancer institute(Key Laboratory of cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical research Center for cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical sciences Zhejang ProvinceChina research Center for life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

AKT2^(S128)/CCTα^(S315/319/323)-positive cancer-associated fibroblasts (CAFs) mediate focal adhesion kinase (FAK) inhibitors resistance via secreting phosphatidylcholines (PCs)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 782-796页

作者： Jie Chen Lingyuan Zhang Yuheng Zhu Di Zhao Jing Zhang Yanmeng Zhu Jingyuan Pang Yuanfan Xiao Qingnan Wu Yan Wang Qimin Zhan Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&Institute100142 BeijingChina Peking University International cancer institute Peking University100191 BeijingChina research Unit of Molecular cancer research Chinese Academy of Medical SciencesBeijingChina Soochow University cancer institute Suzhou 215000China institute of cancer research Shenzhen Bay LaboratoryShenzhen 518107China

Abnormal metabolism is regarded as an oncogenic hallmark related to tumor progression and therapeutic *** study employed multi-omics,including phosphoproteomics,untargeted metabolomics and lipidomics,to demonstrate that the pAKT2 Ser128 and pCCTαSer315/319/323-positive cancer-associated fibroblasts(CAFs)substantially release phosphatidylcholines(PCs),contributing to the resistance of focal adhesion kinase(FAK)inhibitors in esophageal squamous cell carcinoma(ESCC)***,we observed extremely low levels of FAK Tyr397 expression in CAFs,potentially offering no available target for FAK inhibitors playing their anti-growth role in ***,FAK inhibitor increased the intracellular concentration of Ca2+in CAFs,promoting the formation of AKT2/CCTαcomplex,leading to phosphorylation of CCTαSer315/319/323 sites and eventually enhancing stromal PC *** activation could stimulate the intratumoral Janus kinase 2(JAK2)/Signal transducer and activator of transcription 3(STAT3)pathway,triggering resistance to FAK *** of clinical samples demonstrated that stromal pAKT2 Ser128 and pCCTαSer315/319/323 are related to the tumor malignancy and reduced patient ***-targeted lipidomics and further validation cohort quantitatively showed that plasma PCs enable to distinguish the malignant extent of ESCC *** conclusion,inhibition of stroma-derived PCs and related pathway could be possible therapeutic strategies for tumor therapy.

关键词： CAFs metabolism resistance

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National Science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for Brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of life sciences University of Science and Technology of China institute of Semiconductors Chinese Academy of Sciences Department of Modern life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong institute of Brain Science-Shenzhen Fundamental research Institutions Suzhou institute for Advanced research University of Science and Technology of China institute of Artiflcial Intelligence Hefei Comprehensive National Science Center

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the ***, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in ***-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

Pathogenic genes associated with Parkinson’s disease:molecular mechanism overview

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BIOCELL 2024年第5期48卷 707-729页

作者： TINGTING LIU YIWEI HAO lifeNG ZHAO School of life sciences Institute for Brain Sciences ResearchHenan UniversityKaifeng475004China Pharmaceutical Department Peking University Cancer Hospital Inner Mongolia HospitalHohhot010010China

Parkinson’s disease(PD)is a common neurodegenerative disease in the elderly,accounting for more than 1%of the population aged 65 *** inheritance is relatively rare in PD,accounting for approximately 5%to 10%of PD patients,and there is a growing body of evidence suggesting that multiple genetic risk factors play a significant role in the pathogenesis of *** groups have identified and reported a number of genes carrying mutations associated with affected family *** genes associated with PD are also candidates for idiopathic PD,and these genes may also carry other mutation sites that increase *** multiple genetic risk factors are combined,the risk of PD is increased to a greater extent,and to unravel the pathogenic pathways that lead to different forms of *** review focuses on the association of PD genes,such as Parkinson Disease 1-24(PARK1-24),glucosylceramidase(GBA),GTP cyclohydrolase 1(GCH1),fibroblast growth factor 20(FGF20),nuclear receptor-related factor 1(NURR1),NUS1 dehydrodolichyl diphosphate synthase subunit(NUS1),diacylglycerol Lipase Beta(DAGLB),transmembrane protein(TMEM),ubiquinol-cytochrome c reductase core protein 1(UQCRC1),glycoprotein non-metastatic melanoma protein B protein(GPNMB),dynactin 1(DCTN1),LDL receptor related protein 10(LRP10),monoamine oxidase(MAO),ataxin 2(ATXN2),microtubule associated protein tau(MAPT),pantothenate kinase 2(PANK2),spastic parapplegia type 11(SPG11),polymer gamma(POLG),TATA-box binding protein associated factor 1(TAF1),dual specificity tyrosine phosphorylation regulated kinase 1A(Dyrk1a),and crystallin alpha A(CRYAA),with the pathogenesis of *** introduce what is currently known about the molecular genetics of PD to help explain the molecular mechanisms leading to the neurodegenerative disease.

关键词： Parkinson’s disease(PD) Molecular genetics Mutation

Rice ONAC016 promotes leaf senescence through abscisic acid signaling pathway involving OsNAP

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The Crop Journal 2024年第3期12卷 709-720页

作者： Eunji Gi Sung-Hwan Cho Suk-Hwan Kim Kiyoon Kang Nam-Chon Paek Department of Agriculture Forestry and BioresourcesPlant Genomics and Breeding InstituteResearch Institute of Agriculture and Life SciencesSeoul National UniversitySeoul 08826Republic of Korea Division of life sciences Incheon National UniversityIncheon 22012Republic of Korea

Senescence-induced NAC(senNAC)TFs play a crucial role in senescence during the final stage of leaf *** this study,we identified a rice senNAC,ONAC016,which functions as a positive regulator of leaf *** expression of ONAC016 increased rapidly in rice leaves during the progression of dark-induced and natural *** onac016-1 knockout mutant showed a delayed leaf yellowing phenotype,whereas the overexpression of ONAC016 accelerated leaf ***,ONAC016 expression was upregulated by abscisic acid(ABA),and thus detached leaves of the onac016-1 mutant remained green much longer under ABA *** RT-PCR analysis showed that ONAC016 upregulates the genes associated with chlorophyll degradation,senescence,and ABA *** one-hybrid and dual-luciferase assays revealed that ONAC016 binds directly to the promoter regions of OsNAP,a key gene involved in chlorophyll degradation and ABA-induced *** together,these results suggest that ONAC016 plays an important role in promoting leaf senescence through the ABA signaling pathway involving OsNAP.

关键词： Rice ONAC016 OsNAP Leaf senescence Abscisic acid signaling

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Anti-obesity effects of fucoidan from Sargassum thunbergii in adipocytes and high fat diet induced obese mice through inhibiting adipogenic specific transcription factor

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Food Science and Human Wellness 2024年第3期13卷 1608-1616页

作者： Hyo-Geun Lee H.H.A.C.K.Jayawardhana Fengqi Yang D.P.Nagahawaththa N.M.Liyanage Kyung-Mo Song Yun-Sang Choi Seung-Hong Lee You-Jin Jeon Min-Cheol Kang Department of Marine life sciences Jeju National UniversityJeju 63243Republic of Korea Marine Science institute Jeju National UniversityJeju 63333Republic of Korea research Group of Food Processing Korea Food Research InstituteWanju 55365Republic of Korea Department of Pharmoceutical Engineering Soonchunhyang UniversityAsan 31538Republic of Korea

The prevalence of obesity has increased and is a health concern *** to the concerns regarding synthetic anti-obesity treatments,nowadays natural products become a *** studies proved that there is a potential to use marine algae as anti-obesity ***,in this study,the lipid inhibitory effect of crude polysaccharide of amyloglucosidase-assisted hydrolysate from Sargassum thunbergii(STAC)and its fucoidan fractions(STAFs)on 3T3-L1 cells and high-fat diet(HFD)-induced obese mice were *** to the results,the STAF3,showed the highest xylose content and exhibited significant inhibitory effects on lipid accumulation by downregulating adipogenic and lipogenic proteins in 3T3-L1 ***,oral supplementation with STAC significantly declined gain in body weight and fat weight,and serum lipid contents in an HFD-induced obesity mouse *** and chemical characterizations demonstrated that puritied STAF3 has consistent surface morphology and small particle size,with similar structural characteristics as commercial ***,these results indicate that STAC and purified STAF3 from Sargassum thunbergia is a potent source to develop as ananti-obesity agents or functional food products to counter obesity.

关键词： Sargassum thunbergii Fucoidan Anti-obesity Anti-steatosis

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Mobility of rhenium and selenium during chemical weathering and their implication for petrogenic organic carbon oxidation

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Science China Earth sciences 2024年第3期67卷 740-750页

作者： Yuhong ZHANG Jin WANG Yuanxin QU Chao ZHU Zhangdong JIN State Key Laboratory of Loess and Quaternary Geology Institute of Earth EnvironmentChinese Academy of SciencesXi'an 710061China University of Chinese Academy of sciences Beijing 100049China Xi'an institute for innovative Earth Environment research Xi'an 710061China institute of Global Environmental Change Xi'an Jiaotong UniversityXi'an 710049China

The oxidative weathering of petrogenic organic carbon(OC_(petro)) is an important source of carbon dioxide(CO_(2)) into the atmosphere on geological timescales and significantly influences the carbon cycle and global climate change. However, at present, a robust proxy to assess OC_(petro)oxidation is lacking. Riverine rhenium(Re) has emerged as a potential proxy to trace OC_(petro)oxidation, but little is known about Re sources and its relationship with OC_(petro)oxidation. To better understand the robustness of this proxy, we analyzed a shale weathering profile from the early Cambrian Shuijingtuo Formation in Chengkou County, Chongqing City, to address the mobility of Re and selenium(Se) and their relationship with the oxidation of OC_(petro)by analyses of the elemental variation and sequential extraction. The results showed that the chemical index of alteration(CIA)increases from the fresh bedrock to the weathered sections, indicating enhanced weathering intensity. Based on the sequential extraction and mass transfer coefficients(τ), Re and Se mainly exist in the organic phase of shale and are paired lost with OC_(petro) during weathering, with no obvious correlation with sulfide minerals. Furthermore, the different proportions of Re and Se loss with OC_(petro) loss can be attributed to their different geochemical behaviors during weathering. Our study supports Re as a robust proxy to trace OC_(petro) oxidation, whereas Se is the potential one. In the future, combined studies on various sedimentary rock profiles with catchment basins are needed to determine the sources of riverine Re and Se and their relationships with OC_(petro) oxidation.

关键词： Rhenium and selenium Shale Mobility OC_(petro) Chemical weathering

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