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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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

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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

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark l.Dell’Acqua Brian M.Cox Fereshteh s.Nugent Uniformed services University of the Health sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of Methodology 2025年第1期15卷 20-25页

作者： Nadeesha R samarasinghe Taniya s Nagpal Michele l Barbeau Charys M Martin Division of General surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MsK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MsK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of MsK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement MsK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： Medical education Musculoskeletal Anatomy Exercise Online learning

What′s new with the XYZ mesons?

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Chinese Physics C 2008年第6期32卷 455-462页

作者： s.l.Olsen Institute of High Energy Physics Chinese Academy of Sciences

I review some of the recent experimental results on the so-called XYZ mesons.

关键词： charmonium multiquark mesons quark-gluon hybrids

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic lydia Jiménez-Díaz Juan D.Navarro-lópez NeuroPhysiology&Behavior lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Relevance of early intervention in Fahr's disease: understanding through a case study

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General Psychiatry 2019年第1期32卷 43-45页

作者： Jamshed Ahmad Bandna Gupta sujita Kumar kar Department of Psychiatry King George's Medical UniversityLucknowUttar PradeshIndia

sUMMARY Intracranial calcification may result from disturbances in calcium metabolism. It often remains asymptomatic, but may present with symptoms like seizure and neurological deficits. Correction of the underlying metabolic disturbance before damage of neuronal tissues due to intracranial calcification may be useful in preventing irreversible neurological deficits. This window period may be the crucial period that needs a thorough clinical evaluation and urgent intervention. We highlight the case of an adult woman with Fahr's disease presented with generalised tonic-clonic seizure. The management priorities were also discussed along with review of literature.

关键词： Relevance of early intervention Fahr's disease understanding through a case study

Immunoprophylactic potential of filarial glutathione-s-transferase in lymphatic filariaisis

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Asian Pacific Journal of Tropical Medicine 2011年第3期4卷 185-191页

作者： Madhusmita Bal Mandal N Achary KG Das MK kar sK Division of Immunology Regional Medical Research Centre(Indian Council of Medical Research) ChandrasekharpurBhubaneswar-751023India

Objective:To elucidates the immunoprophylactic potential of glutathion-s-transferase(GsT) from cattle filarial parasite setaria digitata(***) against lymphatic ***: GsT was purified through affinity chromatography(sdGsT) and chacterized by sDs-PAGE and Nano-lC Ms/Ms *** isotypes to sdGsT were measured by *** dependant cellular cytotoxicity(ADCC) was performed in vitro using sera from immunized animals and immune individuals.T-cell proliferation and cytokine response to sdGsT in different groups of filariasis were *** potential of sdGsT was evaluate in animal ***:sdGsT exhibited 30-fold enhancement of enzyme activity over crude parasitic *** was found to be 26 kDa by *** lC-Ms/Ms analysis followed by blast search showed 100%homology with Dirqfilaria immitis(***) and only 43%with Homo sapiens(***).Immunoblotting analysis showed putatively immune individuals carry significant level of antibodies to sdGsT as compared with *** sera and sera endemic normal could neutralize the enzymatic activity of sdGsT and inducing in vitro cytotoxicity of *** blood mononuclear cells(PBMC) from endemic normals upon stimulation with sdGsT showed a mixed type of Th1/Th2 *** immunization clear microfilariae from circulation in *** implanted ***:The heterologous GsT could be potentially developed as a vaccine candidate against lymphatic filarial parasite.

关键词： Glutathione-s-transferase setaria digitata lymphatic filariasis