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ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

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Bone research 2024年第2期12卷 453-468页

作者： Lei Xiong Hao-Han Guo Jin-Xiu Pan Xiao Ren Daehoon Lee Li Chen Lin Mei Wen-Cheng Xiong Department of neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Louis Stoke VA Medical center ClevelandOH 44106USA

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and *** how Wnt/β-catenin signaling is regulated in OBs remain ***6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling ***,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone *** we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone *** knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone *** and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not *** cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

关键词： LRP6 impaired organs

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A systematic review of salivary biomarkers in Parkinson's disease

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Neural Regeneration research 2024年第12期19卷 2613-2625页

作者： Maria Ilenia De Bartolo Daniele Belvisi Romina Mancinelli Matteo Costanzo Claudia Caturano Giorgio Leodori Alfredo Berardelli Giovanni Fabbrini Giorgio Vivacqua IRCCS Neuromed PozzilliItaly Department of Human neurosciences Sapienza University of RomeRomeItaly Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly Department of Experimental Morphology and Microscopy-Integrated research center(PRAAB)-Campus Biomedico University of Rome RomeItaly

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying *** the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection *** represents an easily accessible biofluid and an incredibly wide source of molecular *** the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of *** screening and exclusion,34 relevant articles were derived fo r systematic ***-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's *** alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network

关键词： alpha-synuclein amyloid-beta autophagy DJ-1 neurodegeneration neuroinflammation Parkinson's disease salivary biomarkers tau

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Lactate is a potentially harmful substitute for brain glucose fuel:consequences for metabolic restoration of neurotransmission

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Neural Regeneration research 2025年第5期20卷 1403-1404页

作者： Oliver Kann Lennart Soder Babak Khodaie Institute of Physiology and Pathophysiology Heidelberg UniversityHeidelbergGermany Interdisciplinary center for neurosciences(IZN) Heidelberg UniversityHeidelbergGermany

The metabolite lactate (L-lactate) can be generated and released by diverse brain cells,including neurons,astrocytes,and oligodendrocytes (Kann,2023;Rae et al.,2024).Lactate production usually requires the degradation of glucose (D-glucose)-and glycogen in astrocytes-to pyruvate by glycolysis and subsequent conversion of pyruvate to lactate by the enzyme lactate dehydrogenase(Figure 1A;Dienel,2019;Rae et al.,2024).

关键词： consequences Figure restoration

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Astrocyte syncytium:from neonatal genesis to aging degeneration

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Neural Regeneration research 2024年第2期19卷 395-396页

作者： Min Zhou Shiying Zhong Alexei Verkhratsky Department of Neuroscience Ohio State University Wexner Medical CenterColumbusOHUSA Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Achücarro Basque center for Neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain Department of neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain

Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).

关键词： degeneration neonatal aging

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Autophagy and circadian rhythms:interactions and clinical implications

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BIOCELL 2024年第1期48卷 33-45页

作者： TIANKAI DI ZHIFEI ZHOU FEN LIU YUJIANG CHEN LULU WANG State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China Department of Stomatology The 969th HospitalJoint Logistics Support Force of the Chinese People’s Liberation ArmyHohhot010000China Department of Stomatology General Hospital of Tibetan Military CommandLhasa850000China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research Clinical Research Center of Shaanxi Province for Dental and Maxillofacial DiseasesDepartment of Pediatric DentistryCollege of StomatologyXi’an Jiaotong UniversityXi’an710000China Department of Neurobiology and Institute of neurosciences School of Basic MedicineFourth Military Medical UniversityXi’an710032China

Autophagy is a widespread biological process that controls cellular growth,survival,development,and *** rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and *** of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian *** has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal *** can modulate circadian rhythms by breaking down proteins that regulate the circadian *** potential regulatory connection between the two has been a popular subject of clinical and fundamental *** the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the *** present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.

关键词： Autophagy Circadian rhythms Mechanism Application

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Small molecular decoys in Alzheimer's disease

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Neural Regeneration research 2024年第8期19卷 1658-1659页

作者： Sho Oasa Valentina L.Kouznetsova Igor F.Tsigelny Lars Terenius Department of Clinical Neuroscience Center for Molecular MedicineKarolinska InstitutetStockholmSweden San Diego Supercomputer center University of California San DiegoLa JollaCAUSA Department of neurosciences University of California San DiegoLa JollaCAUSA Department of Clinical Neuroscience Karolinska University HospitalKarolinska InstitutetStockholmSweden

Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in *** formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.

关键词： Alzheimer decoy Aβ

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Apolipoprotein A-I binding protein-mediated neuroprotection in glaucomatous neuroinflammation and neurodegeneration

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Neural Regeneration research 2025年第5期20卷 1414-1415页

作者： Sinwoo Hwang Seunghwan Choi Soo-Ho Choi Keun-Young Kim Yury I.Miller Won-Kyu Ju Hamilton Glaucoma center and Shiley Eye Institute The Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCAUSA Department of Medicine University of California San DiegoLa JollaCAUSA National center for Microscopy and Imaging research Department of NeurosciencesUniversity of California San DiegoLa JollaCAUSA

Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs *** to the aging population,it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more *** primarily contributes to optic nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs),subsequently leading to vision impairment.

关键词： irreversible pass primarily

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric research center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Spinal dural arteriovenous fistula:a comprehensive review of the history,classification systems,management,and prognosis

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Chinese Neurosurgical Journal 2024年第1期10卷 48-56页

作者： Ali Alkhaibary Ahoud Alharbi Nada Alnefaie Hajar Alammar Alshaymaa M.Arishy Noor Alghanim Yazeed M.Aldhfyan Arwa Albaiahy Yahya H.Khormi Wael Alshaya Saad AlQahatani Ahmed Aloraidi Ahmed Alkhani Sami Khairy College of Medicine King Saud Bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia King Abdullah International Medical research center RiyadhSaudi Arabia Division of Neurosurgery Department of SurgeryKing Abdulaziz Medical CityMinistry of National Guard-Health AffairsRiyadhSaudi Arabia Department of Neurosurgery National Neurosciences InstituteKing Fahad Medical CityRiyadhSaudi Arabia College of Medicine Jazan UniversityJazanSaudi Arabia Department of Neurosurgery King Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia Department of Surgery Faculty of MedicineJazan UniversityJazanSaudi Arabia

Spinal dural arteriovenous fistulas account for the majority of spinal vascular *** are typically located in the thoracolumbar region and are diagnosed in the middle-aged and elderly *** spinal dural arteriovenous fistulas have been postulated to be acquired,their exact development remains ***,the arteriovenous shunt is situated close to the spinal nerve root,inside the dura mater,where the blood from the radiculomeningeal artery and radicular vein *** history,there have been multiple classification systems of spinal arteriovenous shunts since *** were mainly based on the evolution of diagnostic studies as well as the treatment of these *** classification systems have undergone significant changes over the *** intracranial dural arteriovenous fistula,spinal dural arteriovenous fistula is progressive in *** neurological manifestations,due to venous congestion,tend to be insidious as well as *** include sensory deficits,such as paresthesia,bilateral and/or unilateral radicular pain affecting the lower limbs,and gait *** dural arteriovenous fistulas can be suspected on magnetic resonance imaging/magnetic resonance angiography and confirmed by digital subtraction angiography(DSA).The management includes surgery,endovascular therapy,and in selected cases,*** treatment goal of spinal dural arteriovenous fistula is to halt the progression of the *** prognosis depends on both the duration of symptoms as well as the clinical condition prior to *** present article comprehensively reviews the pathophysiology,changes in classification systems,natural history,clinical manifestations,radiological features,management,and prognosis.

关键词： Connection Endovascular Myelopathy Vascular

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