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Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper Amsterdam UMC location Vrije Universiteit Amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model

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neuroscience Bulletin 2024年第6期40卷 707-718页

作者： Dengcheng Zhan Jingjing Zhang Songxue Su Xiuhua Ren Sen Zhao Weidong Zang Jing Cao department of human Anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China neuroscience Research Institute Zhengzhou UniversityZhengzhou450001China

Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely *** this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in *** found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory *** involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or ***,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like ***,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical *** data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.

关键词： Facial pain KCNQ2 potassium channel TET1 protein

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

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

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

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

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

Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans:an overview of recent findings

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Neural Regeneration Research 2024年第9期19卷 1908-1918页

作者： Marcello Serra Nicola Simola Alexia E.Pollack Giulia Costa department of Biomedical Sciences Section of NeuroscienceUniversity of CagliariCagliariItaly department of Biology University of Massachusetts-BostonBostonMAUSA

Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic *** toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and *** present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and *** elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.

关键词： 3,4-methylenedioxymethamphetamine amphetamine caffeine cell cultures cocaine methamphetamine methylphenidate neurotoxicity nicotine

A perspective on age-related changes in cell environment and risk of neurodegenerative diseases

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Neural Regeneration Research 2024年第4期19卷 719-720页

作者： Alice Y.Liu department of Cell Biology and neuroscience Rutgers State University of New JerseyPiscatawayNJUSA

“Age-related neurodegenerative disease”underscores human age as the primary risk factor for disease development:Alzheimer’s,Parkinson’s,and Huntington’s disease(HD)as *** for the age-dependent delay in disease manifestation,in particular for autosomal dominant forms of the disease,and the underlying cause(s)of specific neuron dysfunction and death to manifest as memory loss,anxiety,depression,and agitation in disease subjects remain *** are interested in understanding age-related changes in cell environment that can modulate the structure,function,aggregation.

关键词： Huntington Alzheimer death