Neuronal signaling最新文献_第3页

Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine. 靶向多巴胺高亲和转运体的兴奋性新型精神活性物质的分子作用机制。

Neuronal signaling Pub Date : 2021-11-17 eCollection Date: 2021-12-01 DOI: 10.1042/NS20210006

Michelle A Sahai, Jolanta Opacka-Juffry

{"title":"Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine.","authors":"Michelle A Sahai, Jolanta Opacka-Juffry","doi":"10.1042/NS20210006","DOIUrl":"10.1042/NS20210006","url":null,"abstract":"Drug misuse is a significant social and public health problem worldwide. Misused substances exert their neurobehavioural effects through changing neural signalling within the brain, many of them leading to substance dependence and addiction in the longer term. Among drugs with addictive liability, there are illicit classical stimulants such as cocaine and amphetamine, and their more recently available counterparts known as novel psychoactive substances (NPS). Stimulants normally increase dopamine availability in the brain, including the pathway implicated in reward-related behaviour. This pattern is observed in both animal and human brain. The main biological target of stimulants, both classical and NPS, is the dopamine transporter (DAT) implicated in the dopamine-enhancing effects of these drugs. This article aims at reviewing research on the molecular mechanisms underpinning the interactions between stimulant NPS, such as benzofurans, cathinones or piperidine derivatives and DAT, to achieve a greater understanding of the core phenomena that decide about the addictive potential of stimulant NPS. As the methodology is essential in the process of experimental research in this area, we review the applications of in vitro, in vivo and in silico approaches. The latter, including molecular dynamics, attracts the focus of the present review as the method of choice in molecular and atomistic investigations of the mechanisms of addiction of stimulant NPS. Research of this kind is of interest to not only scientists but also health professionals as updated knowledge of NPS, their modes of action and health risks, is needed to tackle the challenges posed by NPS misuse.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 4","pages":"NS20210006"},"PeriodicalIF":0.0,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39710118","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: 2

A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment. 棘手的情况：蛋白质棕榈酰化的调节和功能，重点关注轴突和轴突起始段。

Neuronal signaling Pub Date : 2021-10-06 eCollection Date: 2021-12-01 DOI: 10.1042/NS20210005

Andrey A Petropavlovskiy, Jordan A Kogut, Arshia Leekha, Charlotte A Townsend, Shaun S Sanders

{"title":"A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment.","authors":"Andrey A Petropavlovskiy, Jordan A Kogut, Arshia Leekha, Charlotte A Townsend, Shaun S Sanders","doi":"10.1042/NS20210005","DOIUrl":"10.1042/NS20210005","url":null,"abstract":"In neurons, the axon and axon initial segment (AIS) are critical structures for action potential initiation and propagation. Their formation and function rely on tight compartmentalisation, a process where specific proteins are trafficked to and retained at distinct subcellular locations. One mechanism which regulates protein trafficking and association with lipid membranes is the modification of protein cysteine residues with the 16-carbon palmitic acid, known as S-acylation or palmitoylation. Palmitoylation, akin to phosphorylation, is reversible, with palmitate cycling being mediated by substrate-specific enzymes. Palmitoylation is well-known to be highly prevalent among neuronal proteins and is well studied in the context of the synapse. Comparatively, how palmitoylation regulates trafficking and clustering of axonal and AIS proteins remains less understood. This review provides an overview of the current understanding of the biochemical regulation of palmitoylation, its involvement in various neurological diseases, and the most up-to-date perspective on axonal palmitoylation. Through a palmitoylation analysis of the AIS proteome, we also report that an overwhelming proportion of AIS proteins are likely palmitoylated. Overall, our review and analysis confirm a central role for palmitoylation in the formation and function of the axon and AIS and provide a resource for further exploration of palmitoylation-dependent protein targeting to and function at the AIS.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 4","pages":"NS20210005"},"PeriodicalIF":0.0,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39526158","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: 4

The immunogenicity of midbrain dopaminergic neurons and the implications for neural grafting trials in Parkinson's disease. 中脑多巴胺能神经元的免疫原性及其对帕金森病神经移植试验的影响。

Neuronal signaling Pub Date : 2021-09-13 eCollection Date: 2021-09-01 DOI: 10.1042/NS20200083

Shamma Qarin, Sarah K Howlett, Joanne L Jones, Roger A Barker

引用次数: 0

Cannabidiol modulation of oxidative stress and signalling. 大麻二酚调节氧化应激和信号传导。

Neuronal signaling Pub Date : 2021-08-24 eCollection Date: 2021-09-01 DOI: 10.1042/NS20200080

Sónia R Pereira, Becky Hackett, David N O'Driscoll, Melody Cui Sun, Eric J Downer

{"title":"Cannabidiol modulation of oxidative stress and signalling.","authors":"Sónia R Pereira, Becky Hackett, David N O'Driscoll, Melody Cui Sun, Eric J Downer","doi":"10.1042/NS20200080","DOIUrl":"https://doi.org/10.1042/NS20200080","url":null,"abstract":"Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates that CBD can regulate redox function at multiple levels, with a range of downstream effects on cells and tissues. However, pro-oxidant capacity of CBD has also been reported, and hence caution must be applied when considering CBD from a therapeutic standpoint. Such pro- and antioxidant functions of CBD may be cell- and model-dependent and may also be influenced by CBD dose, the duration of CBD treatment and the underlying pathology.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 3","pages":"NS20200080"},"PeriodicalIF":0.0,"publicationDate":"2021-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39414754","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: 24

Oligodendrocytes in the aging brain. 衰老大脑中的少突胶质细胞。

Neuronal signaling Pub Date : 2021-07-06 eCollection Date: 2021-09-01 DOI: 10.1042/NS20210008

Eleanor Catherine Sams

{"title":"Oligodendrocytes in the aging brain.","authors":"Eleanor Catherine Sams","doi":"10.1042/NS20210008","DOIUrl":"10.1042/NS20210008","url":null,"abstract":"More than half of the human brain volume is made up of white matter: regions where axons are coated in myelin, which primarily functions to increase the conduction speed of axon potentials. White matter volume significantly decreases with age, correlating with cognitive decline. Much research in the field of non-pathological brain aging mechanisms has taken a neuron-centric approach, with relatively little attention paid to other neural cells. This review discusses white matter changes, with focus on oligodendrocyte lineage cells and their ability to produce and maintain myelin to support normal brain homoeostasis. Improved understanding of intrinsic cellular changes, general senescence mechanisms, intercellular interactions and alterations in extracellular environment which occur with aging and impact oligodendrocyte cells is paramount. This may lead to strategies to support oligodendrocytes in aging, for example by supporting myelin synthesis, protecting against oxidative stress and promoting the rejuvenation of the intrinsic regenerative potential of progenitor cells. Ultimately, this will enable the protection of white matter integrity thus protecting cognitive function into the later years of life.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 3","pages":"NS20210008"},"PeriodicalIF":0.0,"publicationDate":"2021-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39206890","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: 28

Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction. 利用α-klotho的神经保护作用来解决衰老和神经退行性相关的认知功能障碍。

Neuronal signaling Pub Date : 2021-06-14 eCollection Date: 2021-06-01 DOI: 10.1042/NS20200101

Kelsey Hanson, Kate Fisher, Nigel M Hooper

{"title":"Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction.","authors":"Kelsey Hanson, Kate Fisher, Nigel M Hooper","doi":"10.1042/NS20200101","DOIUrl":"10.1042/NS20200101","url":null,"abstract":"Cognitive dysfunction is a key symptom of ageing and neurodegenerative disorders, such as Alzheimer's disease (AD). Strategies to enhance cognition would impact the quality of life for a significant proportion of the ageing population. The α-klotho protein may protect against cognitive decline through multiple mechanisms: such as promoting optimal synaptic function via activation of N-methyl-d-aspartate (NMDA) receptor signalling; stimulating the antioxidant defence system; reducing inflammation; promoting autophagy and enhancing clearance of amyloid-β. However, the molecular and cellular pathways by which α-klotho mediates these neuroprotective functions have yet to be fully elucidated. Key questions remain unanswered: which form of α-klotho (transmembrane, soluble or secreted) mediates its cognitive enhancing properties; what is the neuronal receptor for α-klotho and which signalling pathways are activated by α-klotho in the brain to enhance cognition; how does peripherally administered α-klotho mediate neuroprotection; and what is the molecular basis for the beneficial effect of the VS variant of α-klotho? In this review, we summarise the recent research on neuronal α-klotho and discuss how the neuroprotective properties of α-klotho could be exploited to tackle age- and neurodegeneration-associated cognitive dysfunction.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 2","pages":"NS20200101"},"PeriodicalIF":0.0,"publicationDate":"2021-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39127276","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

Mitochondrial and metabolic dysfunction in Friedreich ataxia: update on pathophysiological relevance and clinical interventions. 弗里德里希共济失调的线粒体和代谢功能障碍:病理生理学相关性和临床干预的最新进展。

Neuronal signaling Pub Date : 2021-05-17 eCollection Date: 2021-06-01 DOI: 10.1042/NS20200093

David R Lynch, Garrett Farmer

{"title":"Mitochondrial and metabolic dysfunction in Friedreich ataxia: update on pathophysiological relevance and clinical interventions.","authors":"David R Lynch, Garrett Farmer","doi":"10.1042/NS20200093","DOIUrl":"https://doi.org/10.1042/NS20200093","url":null,"abstract":"Friedreich ataxia (FRDA) is a recessive disorder resulting from relative deficiency of the mitochondrial protein frataxin. Frataxin functions in the process of iron-sulfur (Fe-S) cluster synthesis. In this review, we update some of the processes downstream of frataxin deficiency that may mediate the pathophysiology. Based on cellular models, in vivo models and observations of patients, ferroptosis may play a major role in the pathogenesis of FRDA along with depletion of antioxidant reserves and abnormalities of mitochondrial biogenesis. Ongoing clinical trials with ferroptosis inhibitors and nuclear factor erythroid 2-related factor 2 (Nrf2) activators are now targeting each of the processes. In addition, better understanding of the mitochondrial events in FRDA may allow the development of improved imaging methodology for assessing the disorder. Though not technologically feasible at present, metabolic imaging approaches may provide a direct methodology to understand the mitochondrial changes occurring in FRDA and provide a methodology to monitor upcoming trials of frataxin restoration.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 2","pages":"NS20200093"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38945565","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: 15

Signalling pathways contributing to learning and memory deficits in the Ts65Dn mouse model of Down syndrome. 唐氏综合征Ts65Dn小鼠模型中导致学习和记忆缺陷的信号通路

Neuronal signaling Pub Date : 2021-03-12 eCollection Date: 2021-04-01 DOI: 10.1042/NS20200011

Aimée Freeburn, Robert Gordon Keith Munn

{"title":"Signalling pathways contributing to learning and memory deficits in the Ts65Dn mouse model of Down syndrome.","authors":"Aimée Freeburn, Robert Gordon Keith Munn","doi":"10.1042/NS20200011","DOIUrl":"https://doi.org/10.1042/NS20200011","url":null,"abstract":"Down syndrome (DS) is a genetic trisomic disorder that produces life-long changes in physiology and cognition. Many of the changes in learning and memory seen in DS are reminiscent of disorders involving the hippocampal/entorhinal circuit. Mouse models of DS typically involve trisomy of murine chromosome 16 is homologous for many of the genes triplicated in human trisomy 21, and provide us with good models of changes in, and potential pharmacotherapy for, human DS. Recent careful dissection of the Ts65Dn mouse model of DS has revealed differences in key signalling pathways from the basal forebrain to the hippocampus and associated rhinal cortices, as well as changes in the microstructure of the hippocampus itself. In vivo behavioural and electrophysiological studies have shown that Ts65Dn animals have difficulties in spatial memory that mirror hippocampal deficits, and have changes in hippocampal electrophysiological phenomenology that may explain these differences, and align with expectations generated from in vitro exploration of this model. Finally, given the existing data, we will examine the possibility for pharmacotherapy for DS, and outline the work that remains to be done to fully understand this system.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"5 1","pages":"NS20200011"},"PeriodicalIF":0.0,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25513674","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: 4

The life cycle of voltage-gated Ca²⁺ channels in neurons: an update on the trafficking of neuronal calcium channels. 神经元中电压门控 Ca2+ 通道的生命周期：神经元钙通道迁移的最新进展。

Neuronal signaling Pub Date : 2021-02-23 eCollection Date: 2021-04-01 DOI: 10.1042/NS20200095

Laurent Ferron, Saloni Koshti, Gerald W Zamponi

引用次数: 0

Neuronal Signaling: A reflection on the Biochemical Society's newest journal and an exciting outlook on its next steps. 神经元信号:对生化学会最新期刊的反思和对其下一步的令人兴奋的展望。

Neuronal signaling Pub Date : 2021-02-08 eCollection Date: 2021-04-01 DOI: 10.1042/NS20210007

Aideen M Sullivan, S Clare Stanford

引用次数: 0