Progress in Neurobiology最新文献_第4页

The primate putamen processes cognitive flexibility alongside the caudate and ventral striatum with similar speeds of updating values 灵长类动物壳核与尾状体和腹侧纹状体一起处理认知灵活性，更新值的速度相似。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-12-01 DOI: 10.1016/j.pneurobio.2024.102651

Shin-young An , Seong-Hwan Hwang , Keonwoo Lee, Hyoung F. Kim

{"title":"The primate putamen processes cognitive flexibility alongside the caudate and ventral striatum with similar speeds of updating values","authors":"Shin-young An , Seong-Hwan Hwang , Keonwoo Lee, Hyoung F. Kim","doi":"10.1016/j.pneurobio.2024.102651","DOIUrl":"10.1016/j.pneurobio.2024.102651","url":null,"abstract":"<div><div>The putamen is thought to generate habitual actions by processing value information relayed from the ventral striatum through the caudate nucleus. However, it is a question what value the putamen neurons process and whether the putamen receives serially processed value through the striatal structures. We found that neurons in the primate putamen, caudate, and ventral striatum selectively encoded flexibly updated values for adaptive behaviors with similar learning speeds, rather than stably sustained values for habit. In reversal value learning, rostral striatum neurons dynamically adjusted their responses to object values in alignment with changes in saccade reaction times following reversals. Notably, the value acquisition speeds within trials were similar, proposing a parallel value update in each striatal region. However, in stable value retrieval, most did not encode the values for habitual saccades. Our findings suggest that the rostral striatum including the putamen is selectively involved in the parallel processing of cognitive flexibility.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102651"},"PeriodicalIF":6.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microproteins encoded by short open reading frames: Vital regulators in neurological diseases 短开放阅读框编码的微蛋白：神经系统疾病中的重要调节因子

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-23 DOI: 10.1016/j.pneurobio.2024.102694

Xiao Xiao , Yitian Wang , Tingyu Li , Qiang Wang , Xiaolei Luo , Jingdong Li , Linbo Gao

引用次数: 0

Purinergic-associated immune responses in neurodegenerative diseases 神经退行性疾病中与嘌呤能相关的免疫反应。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-22 DOI: 10.1016/j.pneurobio.2024.102693

Sara Carracedo , Agathe Launay , Paul-Alexandre Dechelle-Marquet , Emilie Faivre , David Blum , Cécile Delarasse , Eric Boué-Grabot

{"title":"Purinergic-associated immune responses in neurodegenerative diseases","authors":"Sara Carracedo , Agathe Launay , Paul-Alexandre Dechelle-Marquet , Emilie Faivre , David Blum , Cécile Delarasse , Eric Boué-Grabot","doi":"10.1016/j.pneurobio.2024.102693","DOIUrl":"10.1016/j.pneurobio.2024.102693","url":null,"abstract":"<div><div>The chronic activation of immune cells can participate in the development of pathological conditions such as neurodegenerative diseases including Alzheimer’s disease (AD), Multiple Sclerosis (MS), Parkinson’s disease (PD), Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS).</div><div>In recent years, compelling evidence indicates that purinergic signaling plays a key role in neuro-immune cell functions. The extracellular release of adenosine 5′-triphosphate (ATP), and its breakdown products (ADP and adenosine) provide the versatile basis for complex purinergic signaling through the activation of several families of receptors. G-protein coupled adenosine A<sub>2A</sub> receptors, ionotropic P2X and G-protein coupled P2Y receptors for ATP and other nucleotides are abundant and widely distributed in neurons, microglia, and astrocytes of the central nervous system as well as in peripheral immune cells. These receptors are strongly linked to inflammation, with a functional interplay that may influence the intricate purinergic signaling involved in inflammatory responses.</div><div>In the present review, we examine the roles of the purinergic receptors in neuro-immune cell functions with particular emphasis on A<sub>2A</sub>R, P2X4 and P2X7 and their possible relevance to specific neurodegenerative disorders. Understanding the molecular mechanisms governing purinergic receptor interaction will be crucial for advancing the development of effective immunotherapies targeting neurodegenerative diseases.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102693"},"PeriodicalIF":6.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics R7 RGS 蛋白对神经元 GIRK 通道信号动态的受体依赖性影响

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-13 DOI: 10.1016/j.pneurobio.2024.102686

Haichang Luo , Allison Anderson , Ikuo Masuho , Ezequiel Marron Fernandez de Velasco , Lutz Birnbaumer , Kirill A. Martemyanov , Kevin Wickman

{"title":"Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics","authors":"Haichang Luo , Allison Anderson , Ikuo Masuho , Ezequiel Marron Fernandez de Velasco , Lutz Birnbaumer , Kirill A. Martemyanov , Kevin Wickman","doi":"10.1016/j.pneurobio.2024.102686","DOIUrl":"10.1016/j.pneurobio.2024.102686","url":null,"abstract":"<div><div>Most neurons are influenced by multiple neuromodulatory inputs that converge on common effectors. Mechanisms that route these signals are key to selective neuromodulation but are poorly understood. G protein-gated inwardly rectifying K<sup>+</sup> (GIRK or Kir3) channels mediate postsynaptic inhibition evoked by G protein-coupled receptors (GPCRs) that signal via inhibitory G proteins. GIRK-dependent signaling is modulated by Regulator of G protein Signaling proteins RGS6 and RGS7, but their selectivity for distinct GPCR-GIRK signaling pathways in defined neurons is unclear. We compared how RGS6 and RGS7 impact GIRK channel regulation by the GABA<sub>B</sub> receptor (GABA<sub>B</sub>R), 5HT<sub>1A</sub> receptor (5HT<sub>1A</sub>R), and A<sub>1</sub> adenosine receptor (A<sub>1</sub>R) in hippocampal neurons. Our data show that RGS6 and RGS7 make non-redundant contributions to GABA<sub>B</sub>R- and 5HT<sub>1A</sub>R-GIRK signaling and compartmentalization and suggest that GPCR-G protein preferences and the substrate bias of RGS proteins, as well as receptor-dependent differences in Gα<sub>o</sub> engagement and effector access, shape GPCR-GIRK signaling dynamics in hippocampal neurons.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102686"},"PeriodicalIF":6.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CB1 receptors in NG2 cells mediate cannabinoid-evoked functional myelin regeneration NG2 细胞中的 CB1 受体可介导由 CANNABINOID 引起的功能性髓鞘再生。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-09 DOI: 10.1016/j.pneurobio.2024.102683

Aníbal Sánchez de la Torre , Sara Ezquerro-Herce , Alba Huerga-Gómez , Ester Sánchez-Martín , Juan Carlos Chara , Carlos Matute , Krisztina Monory , Susana Mato , Beat Lutz , Manuel Guzmán , Tania Aguado , Javier Palazuelos

{"title":"CB1 receptors in NG2 cells mediate cannabinoid-evoked functional myelin regeneration","authors":"Aníbal Sánchez de la Torre , Sara Ezquerro-Herce , Alba Huerga-Gómez , Ester Sánchez-Martín , Juan Carlos Chara , Carlos Matute , Krisztina Monory , Susana Mato , Beat Lutz , Manuel Guzmán , Tania Aguado , Javier Palazuelos","doi":"10.1016/j.pneurobio.2024.102683","DOIUrl":"10.1016/j.pneurobio.2024.102683","url":null,"abstract":"<div><div>Defects in myelin homeostasis have been reported in many neuropathological conditions. Cannabinoid compounds have been shown to efficiently promote myelin regeneration in animal models of demyelination. However, it is still unknown whether this action relies mostly on a cell autonomous effect on oligodendroglial-lineage-NG2 cells. By using conditional genetic mouse models, here we found that cannabinoid CB<sub>1</sub> receptors located on NG2 cells are required for oligodendroglial differentiation and myelin regeneration after demyelination. Selective CB<sub>1</sub> receptor gene depletion in NG2 cells following toxin-induced demyelination disrupted oligodendrocyte regeneration and functional remyelination and exacerbated axonal damage. These deficits were rescued by pharmacological blockade of the RhoA/ROCK/Cofilin pathway. Conversely, tetrahydrocannabinol administration promoted oligodendrocyte regeneration and functional remyelination in wild-type but not <em>Ng2</em>-CB<sub>1</sub>-deficient mice. Overall, this study identifies CB<sub>1</sub> receptors as essential modulators of remyelination and support the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102683"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons 尼古丁对下丘脑弓状核 POMC 和 NPY 神经元的相反作用

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102682

E. Ramírez-Sánchez, A. Mondragón-García, J. Garduño, F. Hernández-Vázquez, S. Ortega-Tinoco, S. Hernández-López

{"title":"Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons","authors":"E. Ramírez-Sánchez, A. Mondragón-García, J. Garduño, F. Hernández-Vázquez, S. Ortega-Tinoco, S. Hernández-López","doi":"10.1016/j.pneurobio.2024.102682","DOIUrl":"10.1016/j.pneurobio.2024.102682","url":null,"abstract":"<div><div>The hypothalamic arcuate nucleus (ARC) contains two main populations of neurons essential for energy homeostasis: neuropeptide Y (NPY) neurons, which are orexigenic and stimulate food intake, and proopiomelanocortin (POMC) neurons, which have an anorexigenic effect. Located near the blood-brain barrier, ARC neurons sense blood-borne signals such as leptin, insulin, and glucose. Exogenous substances, such as nicotine, can also alter ARC neuron activity and energy balance. Nicotine, an addictive drug used worldwide, inhibits appetite, and reduces body weight, although its mechanisms in regulating ARC neurons are not well understood. Using electrophysiological techniques in brain slices, we investigated the effects of nicotine on POMC and NPY neurons at physiological glucose concentrations. We found that nicotine increased the firing rate of POMC and inhibited NPY neurons. Additionally, nicotine-enhanced glutamatergic inputs to POMC cells and GABAergic inputs to NPY neurons, mediated by α7 and α4β2 nicotinic acetylcholine receptors (nAChRs), respectively. These findings can contribute to the understanding of the anorexigenic effects of nicotine in smokers.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102682"},"PeriodicalIF":6.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation 安杰尔曼综合征模型小鼠突触可塑性的改变可通过 5-HT7R 刺激得到缓解。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102684

Amelia Pizzella , Eduardo Penna , Yan Liu , Natalia Abate , Enza Lacivita , Marcello Leopoldo , Carla Perrone-Capano , Marianna Crispino , Michel Baudry , Xiaoning Bi

{"title":"Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation","authors":"Amelia Pizzella , Eduardo Penna , Yan Liu , Natalia Abate , Enza Lacivita , Marcello Leopoldo , Carla Perrone-Capano , Marianna Crispino , Michel Baudry , Xiaoning Bi","doi":"10.1016/j.pneurobio.2024.102684","DOIUrl":"10.1016/j.pneurobio.2024.102684","url":null,"abstract":"<div><div>Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It is known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some of the behavioral and neuroplasticity dysfunctions in animal models of Fragile X and Rett syndrome, two pathologies associated with ASD. In view of these observations, we hypothesised that alterations of 5-HT7R signalling might also be involved in AS. To test this hypothesis, we stimulated 5-HT7R with the selective agonist LP-211 to investigate its possible beneficial effects on synaptic dysfunctions and altered behavior in the AS mice model. In mutant mice, we observed impairment of the synaptic machinery of protein synthesis, which was reversed by 5-HT7R activation. Moreover, stimulation of 5-HT7R was able to: i) enhance dendritic spine density in hippocampal neurons, which was reduced in AS mice; ii) restore impaired long-term potentiation (LTP) in hippocampal slices of the AS mice; iii) improve cognitive performance of the mutant animals subjected to the fear conditioning paradigm. Altogether, our results, showing beneficial effects of 5-HT7R stimulation in restoring molecular and cognitive deficits associated with AS, suggest that targeting 5-HT7R could be a promising therapeutic approach for the pathology.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102684"},"PeriodicalIF":6.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebellar impairments in genetic models of autism spectrum disorders: A neurobiological perspective 自闭症谱系障碍遗传模型中的小脑损伤：神经生物学视角

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102685

Konstantin Yenkoyan , Artem Grigoryan , Viera Kutna , Susan Shorter , Valerie B. O’Leary , Reza Asadollahi , Saak V. Ovsepian

{"title":"Cerebellar impairments in genetic models of autism spectrum disorders: A neurobiological perspective","authors":"Konstantin Yenkoyan , Artem Grigoryan , Viera Kutna , Susan Shorter , Valerie B. O’Leary , Reza Asadollahi , Saak V. Ovsepian","doi":"10.1016/j.pneurobio.2024.102685","DOIUrl":"10.1016/j.pneurobio.2024.102685","url":null,"abstract":"<div><div>Functional and molecular alterations in the cerebellum are among the most widely recognised associates of autism spectrum disorders (ASD). As a critical computational hub of the brain, the cerebellum controls and coordinates a range of motor, affective and cognitive processes. Despite well-described circuits and integrative mechanisms, specific changes that underlie cerebellar impairments in ASD remain elusive. Studies in experimental animals have been critical in uncovering molecular pathology and neuro-behavioural correlates, providing a model for investigating complex disease conditions. Herein, we review commonalities and differences of the most extensively characterised genetic lines of ASD with reference to the cerebellum. We revisit structural, functional, and molecular alterations which may contribute to neurobehavioral phenotypes. The cross-model analysis of this study provides an integrated outlook on the role of cerebellar alterations in pathobiology of ASD that may benefit future translational research and development of therapies.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102685"},"PeriodicalIF":6.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior 操纵核团核心的 radixin 磷酸化可调节风险选择行为。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-20 DOI: 10.1016/j.pneurobio.2024.102681

Myung Ji Kwak , Su Jeong Choi , Wen Ting Cai , Bo Ram Cho , Joonyeup Han , Jong Woo Park , Lars Björn Riecken , Helen Morrison , Se-Young Choi , Wha Young Kim , Jeong-Hoon Kim

{"title":"Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior","authors":"Myung Ji Kwak , Su Jeong Choi , Wen Ting Cai , Bo Ram Cho , Joonyeup Han , Jong Woo Park , Lars Björn Riecken , Helen Morrison , Se-Young Choi , Wha Young Kim , Jeong-Hoon Kim","doi":"10.1016/j.pneurobio.2024.102681","DOIUrl":"10.1016/j.pneurobio.2024.102681","url":null,"abstract":"<div><div>Ezrin-Radixin-Moesin (ERM) proteins are actin-binding proteins that contribute to morphological changes in dendritic spines. Despite their significant role in regulating spine structure, the role of ERM proteins in the nucleus accumbnes (NAcc) is not well known, especially in in the context of risk-reward decision-making. Here, we measured the relationship between synaptic excitation and inhibition (E/I ratio) from medium spiny neurons in the NAcc core obtained in the rat after a rat gambling task (rGT). Then, after surgery of a phosphomimetic pseudo-active mutant form of radixin (Rdx-T564D) in the NAcc core, we examined its role in synaptic plasticity and the accompanying risk-choice behavior in rGT. We found that basal E/I ratio in the NAcc core was higher in risk-averse rats than risk-seeking rats. However, it was significantly reduced in risk-averse rats similar to that in risk-seeking rats in the presence of Rdx-T564D in the NAcc core. Furthermore, the head sizes of spines were shifted in risk-averse rats expressing Rdx-T564D in the NAcc core, similar to those observed in risk-seeking rats. The effects of Rdx-T564D in risk-averse rats were again manifested as behavioral changes, with reduced selection of optimal choices and increased selection of disadvantageous ones. In this study, we demonstrated that manipulation of radixin phosphorylation status in the NAcc core can alter glutamatergic synaptic transmission and spine structure at this site, as well as risk choice behaviors in the rGT. These novel findings illustrate that radixin in the NAcc core plays a significant role in determining risk preference during the rGT.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102681"},"PeriodicalIF":6.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2ALS phenotypes in Drosophila melanogaster 抑制ERO1A可减轻神经元ER压力并改善黑腹果蝇的UBQLN2ALS表型

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-10 DOI: 10.1016/j.pneurobio.2024.102674

Ranchana Yeewa , Apiwat Sangphukieo , Phatcharida Jantaree , Wasinee Wongkummool , Titaree Yamsri , Siwat Poompouang , Parunya Chaiyawat , Luca Lo Piccolo , Salinee Jantrapirom

{"title":"ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2ALS phenotypes in Drosophila melanogaster","authors":"Ranchana Yeewa , Apiwat Sangphukieo , Phatcharida Jantaree , Wasinee Wongkummool , Titaree Yamsri , Siwat Poompouang , Parunya Chaiyawat , Luca Lo Piccolo , Salinee Jantrapirom","doi":"10.1016/j.pneurobio.2024.102674","DOIUrl":"10.1016/j.pneurobio.2024.102674","url":null,"abstract":"<div><div>Modulating the ER stress pathway holds therapeutic promise for neurodegenerative diseases; however, identifying optimal targets remains challenging. In this study, we conducted an unbiased screening to systematically search for commonly up-regulated proteins in ER stress-related neurodegenerative conditions, with endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) emerging as a significant hit. Further experiments conducted in the model organism <em>Drosophila melanogaster</em> demonstrated that elevated levels of <em>Drosophila</em> ERO1A (ERO1L) were indeed detrimental to neurons. Conversely, genetic suppression or pharmacological inhibition of ERO1L activity provided neuroprotection under ER stress and extended the lifespan of flies. To translate these findings, we performed a genetic modifier screening and underscored significant neuroprotective effects against UBQLN2<sup>ALS</sup> pathology. Additionally, administration of the chemical probe inhibitor of ERO1A, known as EN460, enhanced locomotive functions and neuromuscular junction (NMJ) morphology in <em>Drosophila</em> UBQLN2<sup>ALS</sup> model. Mechanistically, targeting ERO1L during environmental or pathological ER stress mitigated proteotoxic stress by lowering either the PERK or IRE1 branches of the unfolded protein response (UPR). These findings suggest ERO1A as a promising therapeutic target in UBQLN2<sup>ALS</sup> and other ER stress-related conditions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102674"},"PeriodicalIF":6.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0