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Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

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Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi Federica Cherchi Alasdair J.Gibb department of neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly department of neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue ***,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy *** neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic *** indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 *** recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose *** demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor *** present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

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Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

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Neural Regeneration Research 2024年第11期19卷 2339-2340页

作者： Valerie M.K.Verge Nataliya Tokarska Justin M.Naniong department of Anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS neuroscience Research Center University of SaskatchewanSaskatoonSKCanada

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to *** efficient and effective repair programs following demyelination is a major goal and challenge in *** MS therapies focus largely on modulating the immune aspects of the disease contributing to *** this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

关键词： sclerosis degeneration damage

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Investigating epithelial-neuronal signaling contribution in visceral pain through colon organoid-dorsal root ganglion neuron co-cultures

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Neural Regeneration Research 2024年第6期19卷 1199-1200页

作者： Francesco Margiotta Lorenzo Di Cesare Mannelli Antonino Morabito Carla Ghelardini Elena Lucarini department of neuroscience PsychologyDrug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology SectionUniversity of FlorenceFlorenceItaly department of neuroscience PsychologyDrug Research and Child Health-NEUROFARBAUniversity of FlorenceFlorenceItaly Meyer Children’s Hospital IRCCS FlorenceItaly

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs),affecting about 20%of the global population(Grundy et al.,2019).Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects,hence the need to identify novel molecular and cellular targets for drug development.

关键词： pain visceral colon

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The physiological role of the unfolded protein response in the nervous system

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Neural Regeneration Research 2024年第11期19卷 2411-2420页

作者： Shuangchan Wu Wensheng Lin department of neuroscience University of MinnesotaMinneapolisMNUSA Institute for Translational neuroscience University of MinnesotaMinneapolisMNUSA

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded *** UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein *** also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum *** research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous ***,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

关键词： myelin neuron oligodendrocyte Schwann cell unfolded protein response

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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

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Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matthias T.Wyss Christine Heuer Marina Herwerth Institute of pharmacology and Toxicology University of ZurichZürichSwitzerland neuroscience Center Zurich(ZNZ) University of Zurich and ETH ZurichZürichSwitzerland Neurology department University Hospital of ZurichZürichSwitzerland

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of *** is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2)with numerous *** the last few decades,there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune ***,signals mediated by P2 receptors have been shown to contribute to immune system-mediated ***,interference with P2 receptors may be a promising strategy for the modulation of immune *** only a few clinical studies have been conducted in isolated entities with limited success,preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune *** the association of P2 receptors with several disorders from this field,the use of P2 receptor antagonists in clinical therapy is still very *** this narrative review,we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune *** then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune *** suramin,a non-specific purinergic inhibitor,as an example,we further show that off-target effects could be responsible for observed effects in immunological settings,which may have interesting ***,we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system P2 receptor inhibitors suramin

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Premature axon-oligodendrocyte interaction contributes to stalling of experimental axon regeneration after injury to the white matter

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Neural Regeneration Research 2024年第3期19卷 469-470页

作者： Ephraim F.Trakhtenberg department of neuroscience University of Connecticut School of MedicineFarmingtonCTUSA

Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal *** development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).

关键词： thereby white injury

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Beyond functional MRI signals:molecular and cellular modifiers of the functional connectome and cognition

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Neural Regeneration Research 2024年第5期19卷 937-938页

作者： Lorenzo Pini Alessandro Salvalaggio Maurizio Corbetta Padova neuroscience Center University of PadovaItaly Veneto Institute of Molecular Medicine VIMMPadovaItaly department of neuroscience University of PadovaItaly

Our brain is constantly *** at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information *** resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance *** technique measures subtle changes in blood flow,volume,and oxygenation that occur over *** vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.

关键词： functional neural measures

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The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3266-3280页

作者： Wenfeng Li Shuming Chen Jing Lang Jing Luo Jiahui Chen Liping Zhang Zhijie Sun Deli Dong department of pharmacology China Pharmaceutical UniversityNanjing 210009China

The drugs extending healthspan in clinic have always been *** is an FDA-approved clinical antiprotozoal *** is rapidly metabolized to tizoxanide after absorption in *** previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and ***,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 ***,both nitazoxanide and tizoxanide improve high glucose-induced shortening of *** *** has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.

关键词： Nitazoxanide Tizoxanide C.elegans Healthspan Lifespan AMPK Akt Mitochondrial uncoupling

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Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao Joshua Kuruvilla Eng-King Tan department of Neurology National Neuroscience InstituteSingaporeSingapore neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune *** et *** Chen et *** provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

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CRABP1-mediated non-canonical retinoic acid signaling in motor neurons and neural stem cells

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Neural Regeneration Research 2024年第6期19卷 1169-1170页

作者： Li-Na Wei department of pharmacology University of Minnesota Medical SchoolMinneapolisMNUSA

Retinoic acid(RA),the active metabolite of vitamin A(the retinoids),elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems(Corcoran et al.,2002).The effects of RA are mediated by two very distinct pathways;the first is manifested in the nucleus by binding to a large family of nuclear RA receptors(RARs)to regulate proper expression of RAtargeted genes.

关键词： canonical spectrum critical

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