检索结果-南通市图书馆

Like a G6-nal:transcriptional control of G-protein coupled receptors during oligodendroglial development

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第7期20卷 2001-2002页

作者： Tim Aberle michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating *** the central nervous system,this role is taken up by *** are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OpCs)during embryonal *** the majority of OpCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OpCs persist as a progenitor ***,the timing of myelination and maintenance of the OpC pool both need to be precisely *** transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OpC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling *** the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental *** insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GpCR)with known relevance in differentiating oligodendrocytes(Yang et al,2016).

关键词： gained insulation conduction

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao michael S.Wolfe Computational Medicine program and Department of pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

NECAB family of neuronal calcium-binding proteins in health and disease

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael J.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu michael Chopp michael Millman Yanfeng Li pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of physics Oakland UniversityRochesterMIUSA Department of pathology Henry Ford HospitalDetroitMIUSA Division of pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan ping Yu Emily Choi michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： John Mitrofanis Jonathan Stone michael R.Hamblin pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Hepatocellular carcinoma recurrence after liver transplant:An Australian single-centre study

在线全文

学校读者我要写书评

暂无评论

World Journal of Transplantation 2025年第1期15卷 105-114页

作者： Matthew G Garas Luis Calzadilla-Bertot Briohny W Smith Luc Delriviere Byron Jaques Lingjun Mou Leon A Adams Gerry C MacQuillan George Garas Gary p Jeffrey michael C Wallace Medical School University of Western AustraliaNedlands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of Surgery Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia

BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths *** transplantation(LT)offers the most effective *** recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for *** rate of HCC recurrence is generally reported as 8%-20%in the *** predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian *** To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT *** We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and *** was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of *** survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier *** and multivariate Cox regression was used to determine predictors of HCC recurrence *** Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 *** median time to recurrence was 2.9 years±0.75 *** comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(p=0.001),vascular invasion(p=0.003)and poorly differentiated HCC(p=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank pporary Australian cohort,however it significantly impacted post-LT *** studies are requir

关键词： Liver cancer Recurrence Liver transplantation Hepatocellular carcinoma predictors post-transplant survival Australian data

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

Satiety testing: Ready for the clinic?

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2008年第35期14卷 5371-5376页

作者： michael p Jones Division of Gastroenterology Northwestern UniversityChicagoIL 60611United States

Drink tests are advocated as an inexpensive, nonivasive technique to assess gastric function in patients with a variety of upper digestive symptoms. Many patients with dyspeptic complaints will achieve satiation or develop symptoms at ingested volumes below those typically required to achieve these endpoints in controls. Substantial variation in test performance exists and a greater degree of standardization is required. Additionally, it remains unclear exactly what drink tests measure as correlations with measures of gastric sensation, accomodation and emptying are modest at best. Finally, results of drink tests do not guide therpay. At present, these tests are best reserved for research studies and are not advocated for use in clinical practice.

关键词： Drink test Dyspepsia Gastroparesis