Neuronal signaling最新文献_第6页

MEF2C and HDAC5 regulate Egr1 and Arc genes to increase dendritic spine density and complexity in early enriched environment. MEF2C和HDAC5调控Egr1和Arc基因，在早期富集环境中增加树突棘密度和复杂性。

Neuronal signaling Pub Date : 2020-07-23 eCollection Date: 2020-09-01 DOI: 10.1042/NS20190147

Shu Juan Puang, Bavani Elanggovan, Tendy Ching, Judy C G Sng

引用次数: 3

The class II histone deacetylases as therapeutic targets for Parkinson's disease. ⅱ类组蛋白去乙酰化酶作为帕金森病的治疗靶点。

Neuronal signaling Pub Date : 2020-06-09 eCollection Date: 2020-06-01 DOI: 10.1042/NS20200001

Martina Mazzocchi, Louise M Collins, Aideen M Sullivan, Gerard W O'Keeffe

{"title":"The class II histone deacetylases as therapeutic targets for Parkinson's disease.","authors":"Martina Mazzocchi, Louise M Collins, Aideen M Sullivan, Gerard W O'Keeffe","doi":"10.1042/NS20200001","DOIUrl":"https://doi.org/10.1042/NS20200001","url":null,"abstract":"Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by specific motor impairments. The neuropathological hallmarks of PD include progressive degeneration of midbrain dopaminergic neurons, and loss of their axonal projections to the striatum. Additionally, there is progressive accumulation and spread of intracellular aggregates of α-synuclein. Although dopamine-replacement pharmacotherapy can treat PD symptoms in the short-term, there is a critical need for the development of disease-modifying therapies based on an understanding of the underlying disease mechanisms. One such mechanism is histone acetylation, which is a common epigenetic modification that alters gene transcription. A number of studies have described alterations in histone acetylation in the brains of PD patients. Moreover, α-synuclein accumulation has been linked to alterations in histone acetylation and pharmacological strategies aimed at modulating histone acetylation are under investigation as novel approaches to disease modification in PD. Currently, such strategies are focused predominantly on pan-inhibition of histone deacetylase (HDAC) enzymes. Inhibition of specific individual HDAC enzymes is a more targeted strategy that may allow for future clinical translation. However, the most appropriate class of HDACs that should be targeted for neuroprotection in PD is still unclear. Recent work has shed new light on the role of class-II HDACs in dopaminergic degeneration. For this reason, here we describe the regulation of histone acetylation, outline the evidence for alterations in histone acetylation in the PD brain, and focus on the roles of class II HDACs and the potential of class-II HDAC inhibition as a therapeutic approach for neuroprotection in PD.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Mechanisms and roles of mitochondrial localisation and dynamics in neuronal function. 线粒体定位和神经元功能动力学的机制和作用。

Neuronal signaling Pub Date : 2020-06-01 DOI: 10.1042/NS20200008

Richard Seager, Laura Lee, Jeremy M Henley, Kevin A Wilkinson

{"title":"Mechanisms and roles of mitochondrial localisation and dynamics in neuronal function.","authors":"Richard Seager, Laura Lee, Jeremy M Henley, Kevin A Wilkinson","doi":"10.1042/NS20200008","DOIUrl":"https://doi.org/10.1042/NS20200008","url":null,"abstract":"Neurons are highly polarised, complex and incredibly energy intensive cells, and their demand for ATP during neuronal transmission is primarily met by oxidative phosphorylation by mitochondria. Thus, maintaining the health and efficient function of mitochondria is vital for neuronal integrity, viability and synaptic activity. Mitochondria do not exist in isolation, but constantly undergo cycles of fusion and fission, and are actively transported around the neuron to sites of high energy demand. Intriguingly, axonal and dendritic mitochondria exhibit different morphologies. In axons mitochondria are small and sparse whereas in dendrites they are larger and more densely packed. The transport mechanisms and mitochondrial dynamics that underlie these differences, and their functional implications, have been the focus of concerted investigation. Moreover, it is now clear that deficiencies in mitochondrial dynamics can be a primary factor in many neurodegenerative diseases. Here, we review the role that mitochondrial dynamics play in neuronal function, how these processes support synaptic transmission and how mitochondrial dysfunction is implicated in neurodegenerative disease.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 50

A role for TGFβ signalling in medium spiny neuron differentiation of human pluripotent stem cells. tgf - β信号在人多能干细胞中棘神经元分化中的作用。

Neuronal signaling Pub Date : 2020-05-06 eCollection Date: 2020-06-01 DOI: 10.1042/NS20200004

Marija Fjodorova, Zoe Noakes, Meng Li

{"title":"A role for TGFβ signalling in medium spiny neuron differentiation of human pluripotent stem cells.","authors":"Marija Fjodorova, Zoe Noakes, Meng Li","doi":"10.1042/NS20200004","DOIUrl":"https://doi.org/10.1042/NS20200004","url":null,"abstract":"Activin A and other TGFβ family members have been shown to exhibit a certain degree of promiscuity between their family of receptors. We previously developed an efficient differentiation protocol using Activin A to obtain medium spiny neurons (MSNs) from human pluripotent stem cells (hPSCs). However, the mechanism underlying Activin A-induced MSN fate specification remains largely unknown. Here we begin to tease apart the different components of TGFβ pathways involved in MSN differentiation and demonstrate that Activin A acts exclusively via ALK4/5 receptors to induce MSN progenitor fate during differentiation. Moreover, we show that Alantolactone, an indirect activator of SMAD2/3 signalling, offers an alternative approach to differentiate hPSC-derived forebrain progenitors into MSNs. Further fine tuning of TGFβ pathway by inhibiting BMP signalling with LDN193189 achieves accelerated MSN fate specification. The present study therefore establishes an essential role for TGFβ signalling in human MSN differentiation and provides a fully defined and highly adaptable small molecule-based protocol to obtain MSNs from hPSCs.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma. 神经母细胞瘤中不同的1型骨形态发生蛋白受体与不同分子通路和存活结果的关联。

Neuronal signaling Pub Date : 2020-04-23 eCollection Date: 2020-04-01 DOI: 10.1042/NS20200006

Amnah M Alshangiti, Sean L Wyatt, Erin McCarthy, Louise M Collins, Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe

{"title":"Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma.","authors":"Amnah M Alshangiti, Sean L Wyatt, Erin McCarthy, Louise M Collins, Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe","doi":"10.1042/NS20200006","DOIUrl":"https://doi.org/10.1042/NS20200006","url":null,"abstract":"Neuroblastoma (NB) is a paediatric cancer that arises in the sympathetic nervous system. Patients with stage 4 tumours have poor outcomes and 20% of high-risk cases have MYCN amplification. The bone morphogenetic proteins (BMPs) play roles in sympathetic neuritogenesis, by signalling through bone morphogenetic protein receptor (BMPR)2 and either BMPR1A or BMPR1B. Alterations in BMPR2 expression have been reported in NB; it is unknown if the expression of BMPR1A or BMPR1B is altered. We report lower BMPR2 and BMPR1B, and higher BMPR1A, expression in stage 4 and in MYCN-amplified NB. Kaplan-Meier plots showed that high BMPR2 or BMPR1B expression was linked to better survival, while high BMPR1A was linked to worse survival. Gene ontology enrichment and pathway analyses revealed that BMPR2 and BMPR1B co-expressed genes were enriched in those associated with NB differentiation. BMPR1A co-expressed genes were enriched in those associated with cell proliferation. Moreover, the correlation between BMPR2 and BMPR1A was strengthened, while the correlation between BMPR2 and BMPR1B was lost, in MYCN-amplified NB. This suggested that differentiation should decrease BMPR1A and increase BMPR1B expression. In agreement, nerve growth factor treatment of cultured sympathetic neurons decreased Bmpr1a expression and increased Bmpr1b expression. Overexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis. The present study shows that expression of distinct BMPRs is associated with different survival outcomes in NB.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Cortical cells are altered by factors including bone morphogenetic protein released from a placental barrier model under altered oxygenation. 胎盘屏障模型在氧饱和度改变的情况下释放的骨形态发生蛋白等因子会改变皮质细胞。

Neuronal signaling Pub Date : 2020-04-09 eCollection Date: 2020-04-01 DOI: 10.1042/NS20190148

Veronica H L Leinster, Thomas J Phillips, Nicola Jones, Sharon Sanderson, Katja Simon, Jon Hanley, Charles Patrick Case

{"title":"Cortical cells are altered by factors including bone morphogenetic protein released from a placental barrier model under altered oxygenation.","authors":"Veronica H L Leinster, Thomas J Phillips, Nicola Jones, Sharon Sanderson, Katja Simon, Jon Hanley, Charles Patrick Case","doi":"10.1042/NS20190148","DOIUrl":"10.1042/NS20190148","url":null,"abstract":"Episodes of hypoxia and hypoxia/reoxygenation during foetal development have been associated with increased risk of neurodevelopmental conditions presenting in later life. The mechanism for this is not understood; however, several authors have suggested that the placenta plays an important role. Previously we found both placentas from a maternal hypoxia model and pre-eclamptic placentas from patients release factors lead to a loss of dendrite complexity in rodent neurons. Here to further explore the nature and origin of these secretions we exposed a simple in vitro model of the placental barrier, consisting of a barrier of human cytotrophoblasts, to hypoxia or hypoxia/reoxygenation. We then exposed cortical cultures from embryonic rat brains to the conditioned media (CM) from below these exposed barriers and examined changes in cell morphology, number, and receptor presentation. The barriers released factors that reduced dendrite and astrocyte process lengths, decreased GABAB1 staining, and increased astrocyte number. The changes in astrocytes required the presence of neurons and were prevented by inhibition of the SMAD pathway and by neutralising Bone Morphogenetic Proteins (BMPs) 2/4. Barriers exposed to hypoxia/reoxygenation also released factors that reduced dendrite lengths but increased GABAB1 staining. Both oxygen changes caused barriers to release factors that decreased GluN1, GABAAα1 staining and increased GluN3a staining. We find that hypoxia in particular will elicit the release of factors that increase astrocyte number and decrease process length as well as causing changes in the intensity of glutamate and GABA receptor staining. There is some evidence that BMPs are released and contribute to these changes.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-coding RNAs in neuropathic pain. 神经性疼痛中的非编码 RNA。

Neuronal signaling Pub Date : 2020-04-01 Epub Date: 2020-04-23 DOI: 10.1042/NS20190099

Theodora Kalpachidou, Kai K Kummer, Michaela Kress

{"title":"Non-coding RNAs in neuropathic pain.","authors":"Theodora Kalpachidou, Kai K Kummer, Michaela Kress","doi":"10.1042/NS20190099","DOIUrl":"10.1042/NS20190099","url":null,"abstract":"Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain in general, and members of the non-coding RNA (ncRNA) family, specifically the short, 22 nucleotide microRNAs (miRNAs) and the long non-coding RNAs (lncRNAs) act as master switches orchestrating both immune as well as neuronal processes. Several chronic disorders reveal unique ncRNA expression signatures, which recently generated big hopes for new perspectives for the development of diagnostic applications. lncRNAs may offer perspectives as candidates indicative of neuropathic pain in liquid biopsies. Numerous studies have provided novel mechanistic insight into the role of miRNAs in the molecular sequelae involved in the pathogenesis of neuropathic pain along the entire pain pathway. Specific processes within neurons, immune cells, and glia as the cellular components of the neuropathic pain triad and the communication paths between them are controlled by specific miRNAs. Therefore, nucleotide sequences mimicking or antagonizing miRNA actions can provide novel therapeutic strategies for pain treatment, provided their human homologues serve the same or similar functions. Increasing evidence also sheds light on the function of lncRNAs, which converge so far mainly on purinergic signalling pathways both in neurons and glia, and possibly even other ncRNA species that have not been explored so far.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38087015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxidized cholesterol species as signaling molecules in the brain: diabetes and Alzheimer's disease. 氧化胆固醇在大脑中作为信号分子:糖尿病和阿尔茨海默病。

Neuronal signaling Pub Date : 2019-12-01 Epub Date: 2019-11-28 DOI: 10.1042/NS20190068

Thaddeus K Weigel, Joshua A Kulas, Heather A Ferris

引用次数: 6

aPKC in neuronal differentiation, maturation and function. aPKC在神经元分化、成熟和功能中的作用。

Neuronal signaling Pub Date : 2019-09-01 Epub Date: 2019-09-23 DOI: 10.1042/NS20190019

Sophie M Hapak, Carla V Rothlin, Sourav Ghosh

引用次数: 10

Autophagy in the mammalian nervous system: a primer for neuroscientists. 哺乳动物神经系统中的自噬现象：神经科学家入门指南。

Neuronal signaling Pub Date : 2019-09-01 Epub Date: 2019-09-11 DOI: 10.1042/NS20180134

Fumi Suomi, Thomas G McWilliams

引用次数: 0