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Copper homeostasis and neurodegenerative diseases

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

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In situ polymerization of poly(3,4-ethylenedioxythiophene)protective layer towards stable zinc anode

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Nano Research 2025年第1期18卷 382-394页

作者： Debin Luo Peng Zhou Xiaowei Lv Panpan Sun Xiaohua Sun Hewei Zhao College of Materials and Chemical Engineering Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion MaterialsChina Three Gorges UniversityYichang 443002China Hubei Three Gorges laboratory Yichang 443007China School of Chemistry Beihang UniversityBeijing 100191China

Aqueous zinc-ion devices are considered promising candidates for energy storage due to their high safety,low cost and relatively high energy ***,the dendrite growth,hydrogen evolution reaction(HER)and corrosion of the zinc anode significantly limit the development of Zn-ion ***,an inexpensive poly(3,4-ethylenedioxythiophene)(PEDOT)protective layer was constructed in situ on the Zn surface using electropolymerization to suppress dendrite growth and side reactions,thereby enhancing the reversibility of *** and theoretical calculations revealed that this hydrophilic protective layer promotes the desolvation process of hydrated Zn^(2+)and facilitates the transport of zinc ions,thus improving the thermodynamic and kinetic properties of Zn^(2+)deposition and inhibiting interfacial side ***,the optimized PEDOT@Zn symmetric battery exhibited a cycling stability exceeding 1250 h at 0.5 mA·cm^(-2)and 0.25 mAh·cm^(-2),with a significantly reduced overpotential(from 91.8 to 35 mV).With the assistance of the PEDOT protective layer,the PEDOT@Zn//Cu battery maintained approximately 99.5%Coulombic efficiency after 450 ***-situ scanning electron microscopy(SEM)and in situ optical microscopy characterizations further confirmed that the PEDOT protective layer can effectively suppress the growth of zinc ***,the Zn-ion capacitors assembled by the PEDOT@Zn and activated carbon also demonstrated outstanding cycling stability.

关键词： zinc-ion devices zinc anode poly(3 4-ethylenedioxythiophene)(PEDOT) dendrite desolvation process

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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第01期 249-256页

作者： Qing-Yun Fang Chengyihan Gu Yinghan Chen Wencheng Yan Yong Liang Weipeng Li Chengjian Zhu Jie Han Jin Xie State Key laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State Key laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

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Coagulation indices and fibrinogen degradation products as predictive biomarkers for tumor-node-metastasis staging and metastasis in gastric cancer

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 110-120页

作者： Yi-Qing Shen Qiu-Wan Wei Yi-Ren Tian Yun-Zhi Ling Min Zhang Clinical laboratory Civil Aviation Shanghai HospitalGubei Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200000China Clinical laboratory Tongji Hospital of Tongji UniversityShanghai 200000China

BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and *** with the global average,Asia,notably China,reports disproportionately high GC *** disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised ***,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce *** Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December *** associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were *** Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM ***,abnormal coagulation system activation was closely related to disease *** FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic *** Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.

关键词： Coagulation indexes Fibrinogen degradation products Gastric cancer Tumor-node-metastasis staging Distant metastasis

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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

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Neural Regeneration Research 2025年第9期20卷 2655-2666页

作者： Yiyang Qin Wenzhen Zhu Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua Li Xiao-Jiang Li Su Yang Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong–HongKong–Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto *** mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy *** aggregates alter protein-protein interactions and compromise transcriptional *** this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic *** n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor *** down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor *** findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

关键词： androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model neurodegeneration neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor

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BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 214-225页

作者： Qin Wang Qing-Rong Li Lei Xu Zi-Chun Yuan Xiao Liu Mao-Ju Tang Man Luo Xiao-Wu Zhong Qiang Ma Xiao-Lan Guo Department of Clinical laboratory Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of laboratory Medicine&Translational Medicine Research Center North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic *** are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of ***,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for ***150 and KYSE410 cells were cultured and exposed to various concentrations of *** viability was assessed at 48 hours and 72 hours to determine the IC50 *** effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,*** blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,*** values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 ***1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular ***,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 ***1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein *** a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein *** and eosin staining of various organs,including the heart,liver,s

关键词： Esophageal squamous cell carcinoma BIBR1532 Human telomerase reverse transcriptase DNA damage response Telomere-binding proteins

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New aspects of a small GTPase RAB35 in brain development and function

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Neural Regeneration Research 2025年第7期20卷 1971-1980页

作者： Ikuko Maejima Ken Sato laboratory of Molecular Traffic Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or *** processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS *** of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative ***,it is important to understand the physiological and pathological roles of RAB proteins in brain ***35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell ***35 is also involved in neurite outgrowth and turnover of synaptic *** generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and *** mice exhibited defects in anxiety-related behaviors and spatial ***,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal *** contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex *** studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's *** this review,we provide an overview of the current understanding of subcellular functions of *** also provide insights into the phys

关键词： endocytosis endosomes hippocampal development neurodegenerative diseases RAB35

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From text to image:challenges in integrating vision into ChatGPT for medical image interpretation

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Neural Regeneration Research 2025年第2期20卷 487-488页

作者： Shunsuke Koga Wei Du Department of Pathology and laboratory Medicine Hospital of the University of PennsylvaniaPhiladelphiaPAUSA

Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text *** potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical *** ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).

关键词： image diagnosis text

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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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