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Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

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Research 2024年第1期2023卷 735-752页

作者： Daniela Mirzac Svenja L.Kreis Heiko J.Luhmann Gabriel Gonzalez-Escamilla Sergiu Groppa Movement Disorders and Neurostimulation Department of NeurologyFocus Program Translational NeuroscienceRhine Main Neuroscience NetworkUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Physiology University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

Translational experimental approaches that help us better trace Parkinson’s disease(PD)pathophysiological mechanisms leading to new therapeutic targets are urgently *** this article,we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations,as well as their underlying mechanisms and *** aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom’s ***,we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia *** summarize recent achievements extrapolated from available PD animal models,discuss their advantages and limitations,debate on their differential applicability,and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.

关键词： clinical knowledge insight

Interaction between inflammatory bowel disease,physical activity,and myokines:Assessment of serum irisin levels

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World Journal of Gastroenterology 2024年第22期30卷 2923-2926页

作者： Marwan SM Al-Nimer department of Therapeutics and Clinical pharmacology College of MedicineUniversity of DiyalaBaqubah 32001Iraq

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of *** has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those *** is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD *** addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental ***,irisin produces changes in the diversity of the ***,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

关键词： Irisin Inflammatory bowel disease Physical activity Myokines Prognostic marker

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

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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

Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky Center for Brain Research and department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama Center for Brain Research and department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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World Journal of Gastroenterology 2024年第9期30卷 1132-1142页

作者： Antonietta Gerarda Gravina Iacopo Panarese Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico Hepatogastroenterology Division Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Pathology Division Department of Mental and Physical Health and Preventive MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy department of experimental Medicine Division of PharmacologyUniversity of Campania Luigi VanvitelliNaples 80138Italy department of Advanced Medical and Surgical Sciences(DAMSS) University of Campania Luigi VanvitelliNaples 80138Italy department of Pharmacy University of Naples Federico IINaples 80131Italy

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin ***,data regarding their role in inflammatory bowel diseases(IBD)are currently *** This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic *** Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and *** sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,Ppharmacology.

关键词： Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease

Implications of regional identity for neural stem and progenitor cell transplantation in the injured or diseased nervous system

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Neural Regeneration Research 2024年第4期19卷 715-716页

作者： Prakruthi Amar Kumar Jennifer N.Dulin department of Biology Texas A&M UniversityCollege Station Texas A&M Institute for neuroscience Texas A&M UniversityCollege Station

Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.

关键词： neural system injured

Is tuberous sclerosis complex-associated autism a preventable andtreatabledisorder?

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World Journal of Pediatrics 2024年第1期20卷 40-53页

作者： Paolo Curatolo Mirte Scheper Leonardo Emberti Gialloreti Nicola Specchio Eleonora Aronica Child Neurology and Psychiatry Unit Systems Medicine DepartmentTor Vergata UniversityRomeItaly department of Neuropathology Amsterdam NeuroscienceAmsterdam UMC Location University of AmsterdamAmsterdamTheNetherlands department of Biomedicine and Prevention University of Rome Tor VergataVia Montpellier 100133 RomeItaly Clinical and experimental Neurology Bambino Gesù Children's HospitalIRCCSFull Member of European ReferenceNetworkEpiCAREPiazza S.Onofrio400165 RomeItaly Stichting Epilepsie Instellingen Nederland(SEIN) HeemstedeAmsterdamThe Netherlands

Background Tuberous sclerosis complex(TSC)is a genetic disorder caused by inactivating mutations in the TSCl and TSC2 genes,causing overactivation of the mechanistic(previously referred to as mammalian)target of rapamycin(mTOR)signaling pathway in fetal *** mTOR pathway plays a crucial role in several brain processes leading to TSC-related epilepsy,intellectual disability,and autism spectrum disorder(ASD).Pre-natal or early post-natal diagnosis of TSC is now possible in a growing number of pre-symptomatic *** sources We searched PubMed for peer-reviewed publications published between January 2010 and April 2023 with the terms“tuberous sclerosis",“autism",or“autism spectrum disorder""animal models",“preclinical studies",“neurobiology",and“treatment".Results Prospective studies have highlighted that developmental trajectories in TSC infants who were later diagnosed with ASD already show motor,visual and social communication skills in the first year of life *** genetic,cellular,electroencephalography and magnetic resonance imaging biomarkers can identify pre-symptomatic TSC infants at high risk for having autism and *** Preventing epilepsy or improving therapy for seizures associated with prompt and tailored treatment strategies for autism in a sensitive developmental time window could have the potential to mitigate autistic symptoms in infants with TSC.

关键词： Animal model-Autism spectrum disorders Developmental and epileptic encephalopathy Mechanisms mTOR Risk Tuberos sclerosis complex

The Multiple Roles of Autophagy in Neural Function and Diseases

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neuroscience Bulletin 2024年第3期40卷 363-382页

作者： Yan-Yan Li Zheng-Hong Qin Rui Sheng department of pharmacology and Laboratory of Aging and Nervous Diseases Jiangsu Key laboratory of Neuropsychiatric DiseasesCollege of Pharmaceutical Sciences of Soochow UniversitySuzhou 215123China

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes,where proteins,lipids,and organelles are degraded and *** to the way the cytoplasmic components are engulfed,autophagy can be divided into macroautophagy,microautophagy,and chaperone-mediated ***,many studies have found that autophagy plays an important role in neurological diseases,including Alzheimer's disease,Parkinson's disease,Huntington's disease,neuronal excitotoxicity,and cerebral *** maintains cell homeostasis in the nervous system via degradation of misfolded proteins,elimination of damaged organelles,and regulation of apoptosis and ***-mTOR,Beclin 1,TP53,endoplasmic reticulum stress,and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological ***,we discuss the role,functions,and signal pathways of autophagy in neurological diseases,which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

关键词： Autophagy Neurodegenerative diseases Cerebral ischemia AMPK mTOR Beclin 1 TP53 Endoplasmic reticulum stress