Journal of Neurochemistry最新文献

{"title":"EXPRESSION OF CONCERN: Combined Pharmacological, Mutational and Cell Biology Approaches Indicate That p53-Dependent Caspase 3 Activation Triggered by Cellular Prion Is Dependent on Its Endocytosis","authors":"","doi":"10.1111/jnc.70074","DOIUrl":"https://doi.org/10.1111/jnc.70074","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: C. Sunyach and F. Checler, “Combined Pharmacological, Mutational and Cell Biology Approaches Indicate that p53-Dependent Caspase 3 Activation Triggered by Cellular Prion is Dependent on its Endocytosis,” <i>Journal of Neurochemistry</i> 92, no. 6 (2005): 1399–1407, https://doi.org/10.1111/j.1471-4159.2004.02989.x.</p><p>This Expression of Concern is for the above article, published online on 25 February 2005 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Andrew Lawrence; the International Society for Neurochemistry; and John Wiley &amp; Sons Ltd. A third party reported concerns that a portion of the tubulin control in Figure 2a had been manipulated. Additional investigation by the publisher found evidence that the tubulin bands in Figure 4b had been duplicated in Figure 5a. Author F. Checler responded to an inquiry by the publisher and stated that the concerns were unfounded but also stated that the original data were no longer available due to the time that has elapsed since publication and the departure of co-author C. Sunyach from research. The editors have determined that the evidence of image manipulation and duplication casts doubt on the results presented in the article, and that the veracity of the data presented cannot be confirmed due to the lack of original data. Therefore, the journal has decided to issue an Expression of Concern to inform and alert readers. Author F. Checler disagrees with the retraction. Author C. Sunyach could not be reached for comment regarding the Expression of Concern.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts for the Latin American Glia Club Workshop: Paving the Way for Glial Cells Function","authors":"","doi":"10.1111/jnc.70056","DOIUrl":"https://doi.org/10.1111/jnc.70056","url":null,"abstract":"","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKG-Mediated Phosphorylation of TOP2A Activates HDAC to Drive Photoreceptor Cell Death in rd1 Mouse Inherited Retinal Degeneration","authors":"Yujie Dong,&nbsp;Wandong Zuo,&nbsp;Yan Li,&nbsp;Xiaoxiao Feng,&nbsp;Chunming Guo,&nbsp;Maorong Chen,&nbsp;Jie Yan,&nbsp;Chunjiang Hou,&nbsp;Hua Peng,&nbsp;Zhulin Hu,&nbsp;Hai Liu,&nbsp;François Paquet-Durand,&nbsp;Kangwei Jiao","doi":"10.1111/jnc.70077","DOIUrl":"https://doi.org/10.1111/jnc.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Inherited retinal degeneration (IRD) is a debilitating condition characterized by progressive loss of photoreceptor cells. However, the underlying mechanisms remain largely unclear. This study investigated the role of DNA topoisomerase II alpha (TOP2A) and its interplay with protein kinase G (PKG) and histone deacetylase (HDAC) in the <i>rd1</i> mouse model for IRD. Immunofluorescence and quantitative western blotting analyses were performed to evaluate the expression of TOP2A, PKG1, PKG2, HDAC1, and other related markers. TSC24 and suberoylanilide hydroxamic acid were used to specifically inhibit TOP2A and HDAC, respectively, in organotypic retinal explant cultures derived from wild-type or <i>rd1</i> mice. Furthermore, we examined the effect of PKG activity on TOP2A phosphorylation using KT5823. Significant upregulation of TOP2A was observed in the <i>rd1</i> mouse retina compared with wild-type controls, especially in the outer nuclear layer. Phosphorylation levels of TOP2A strongly correlated with photoreceptor cell death. Treatment with TSC24 significantly reduced TOP2A-positive and TUNEL-positive cells. TOP2A phosphorylation was accompanied by HDAC activation, which was mitigated by TSC24. PKG inhibition by KT5823 reduced TOP2A phosphorylation at specific residues and photoreceptor HDAC activity. Our findings position TOP2A in the PKG-TOP2A-HDAC photoreceptor degenerative pathway, offering new potential therapeutic targets for combating IRD-type diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione Metabolism of the Brain—The Role of Astrocytes","authors":"Ralf Dringen,&nbsp;Christian Arend","doi":"10.1111/jnc.70073","DOIUrl":"https://doi.org/10.1111/jnc.70073","url":null,"abstract":"<p>Astrocytes have essential functions in the brain as partners of neurons in many metabolic and homeostatic processes. The metabolism of the tripeptide GSH (γ-L-glutamyl-L-cysteinyl-glycine) is an important example of a metabolic interaction between astrocytes and neurons. GSH is present in brain cells in millimolar concentrations and has essential functions as an antioxidant and as a substrate for detoxification reactions. A high GSH content protects astrocytes against oxidative stress and toxins and is therefore beneficial for the astrocytic self-defense that helps to maintain the essential functions of astrocytes in the brain and will enable astrocytes to eliminate potential toxins before they may reach other brain cells. In addition, astrocytes provide neurons with the amino acids required for GSH synthesis in a process that involves the export of GSH from astrocytes by the multidrug resistance protein 1, the extracellular processing of GSH via the astrocytic γ-glutamyl transpeptidase to generate the dipeptide cysteinyl-glycine, and the extracellular cleavage of this dipeptide by the neuronal ectopeptidase aminopeptidase N. As GSH export from astrocytes strongly depends on the cytosolic GSH concentration, a high astrocytic GSH content will also facilitate GSH release and thereby the supply of GSH precursors to neighboring neurons. In this article, we will give an overview of the current knowledge on the GSH metabolism of astrocytes, address how a high astrocytic GSH content can help to maintain brain functions, and discuss open questions and future perspectives of research on the functions of astrocytes in the GSH metabolism of the healthy and diseased brain.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Power Struggle: Kynurenine Pathway Enzyme Knockouts and Brain Mitochondrial Respiration","authors":"László Juhász,&nbsp;Krisztina Spisák,&nbsp;Boglárka Zsuzsa Szolnoki,&nbsp;Anna Nászai,&nbsp;Ágnes Szabó,&nbsp;Attila Rutai,&nbsp;Szabolcs Péter Tallósy,&nbsp;Andrea Szabó,&nbsp;József Toldi,&nbsp;Masaru Tanaka,&nbsp;Keiko Takeda,&nbsp;Kinuyo Ozaki,&nbsp;Hiromi Inoue,&nbsp;Sayo Yamamoto,&nbsp;Etsuro Ono,&nbsp;Mihály Boros,&nbsp;József Kaszaki,&nbsp;László Vécsei","doi":"10.1111/jnc.70075","DOIUrl":"https://doi.org/10.1111/jnc.70075","url":null,"abstract":"<p>Numerous illnesses, including neurological and mental disorders, have been associated with mitochondrial dysfunction. Disruptions in mitochondrial respiration and energy production have been linked to dysmetabolism of the tryptophan (Trp)-kynurenine (KYN) pathway, which produces a diverse array of bioactive metabolites. Kynurenic acid (KYNA) is a putative neuroprotectant. The exact mechanisms through which Trp-KYN metabolic dysregulation affects mitochondrial function remain largely unclear. This study investigates the impact of the genetic deletion of kynurenine aminotransferase (KAT) enzymes, which are responsible for KYNA synthesis, on mitochondrial function, specifically mitochondrial respiration and ATP synthesis, and its potential role in neuropsychiatric pathology. CRISPR/Cas9-induced knockout mouse strains kat1^−/−, kat2^−/−, and kat3^−/− were generated. Eight-to-ten-week-old male mice were used, and cerebral and hepatic respiration, complex I- and II-linked oxidative phosphorylation (CI and CII OXPHOS), and complex IV (CIV) activity were measured using high-resolution respirometry. Mitochondrial membrane potential changes were measured with Fluorescence-Sensor Blue and safranin dye. KAT knockout mice exhibited significantly lower cerebellar respiration (CI OXPHOS, CII OXPHOS, and CIV activity) compared to wild-type mice. Lower baseline respiration and attenuated OXPHOS activities were observed in the hippocampus and striatum, particularly in kat2^−/− and kat3^−/− mice. Non-neuronal tissues showed reduced CIV activity, while ADP-stimulated CI and CII OXPHOS remained unchanged. The deletion of the KAT genes significantly impairs mitochondrial respiration and ATP synthesis, potentially contributing to pathogenesis. This study highlights the importance of KYNA in mitochondrial function, offering new insights into potential therapeutic targets for various disorders. Targeting the KYN pathway could mitigate mitochondrial dysfunction in a variety of diseased conditions.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgD-CD38-B Cell Partially Mediates the Protective Effect of Higher Serum Triacylglycerol (53:4) Levels Against Parkinson's Disease","authors":"Yajun Jing,&nbsp;Honglin Zhu,&nbsp;Peisen Yao,&nbsp;Yiming Chen,&nbsp;Xuemiao Lai,&nbsp;Qiu He,&nbsp;Lianghong Yu,&nbsp;Yuanxiang Lin,&nbsp;Dezhi Kang","doi":"10.1111/jnc.70067","DOIUrl":"https://doi.org/10.1111/jnc.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Emerging evidence suggests that dysregulated lipid metabolism contributes to Parkinson's disease (PD) risk, with chronic inflammation in the central nervous system (CNS) also playing a pivotal role. Although correlations between inflammatory responses, serum lipid metabolism, and PD risk are established, a causal relationship remains unclear. Building on previous findings linking higher serum triacylglycerol (51:4) levels to reduced PD risk, this study explores the potential causal associations between 38 triacylglycerol isoforms and PD risk using Mendelian randomization (MR). We utilized summary-level data from genome-wide association studies (GWAS) on PD, circulating immune cells, inflammatory proteins, and serum lipidomes—including 38 triacylglycerol isoforms, 15 sterol ester isoforms, and 46 phosphatidylcholine isoforms—to assess the relationship between serum lipid profiles and PD. Our analysis revealed that higher levels of serum triacylglycerol (51:4) and triacylglycerol (53:4) were associated with a reduced PD risk, whereas lower levels of phosphatidylcholine (17:0_18:1) and sterol ester (27:1/20:2) were linked to higher PD risk. Notably, multivariable MR analysis confirmed a robust causal association between increased serum triacylglycerol (53:4) and a 24% reduction in PD risk (1 SD higher triacylglycerol (53:4) leading to a 24% [95% CI, 0.54–0.97] risk reduction, <i>p</i> = 0.005). Mediation analysis suggested that circulating immune cells, rather than inflammatory proteins, may mediate the relationship between triacylglycerol (53:4) levels and PD risk. These findings establish a causal link between triacylglycerol (53:4) and PD risk, highlighting the potential role of immune modulation in PD pathogenesis.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes","authors":"Sean D. Fraser,&nbsp;Remco V. Klaassen,&nbsp;Carmen Villmann,&nbsp;August B. Smit,&nbsp;Robert J. Harvey","doi":"10.1111/jnc.70061","DOIUrl":"https://doi.org/10.1111/jnc.70061","url":null,"abstract":"<p>Glycine receptors (GlyRs) are typically known for mediating inhibitory synaptic transmission within the spinal cord and brainstem, but they also have key roles in embryonic brain development, learning/memory, inflammatory pain sensitization, and rhythmic breathing. GlyR dysfunction has been implicated in multiple neurological disease states, including startle disease (GlyR α1β) and neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), intellectual disability (ID), developmental delay (DD) and epilepsy (GlyR α2). However, GlyRs do not operate in isolation but depend upon stable and transient protein–protein interactions (PPIs) that influence synaptic localization, homeostasis, signaling pathways, and receptor function. Despite the affinity purification of GlyRs using the antagonist strychnine over four decades ago, we still have much to learn about native GlyR stoichiometry and accessory proteins. In contrast to other neurotransmitter receptors, &lt; 20 potential GlyR interactors have been identified to date. These include some well-known proteins that are vital to inhibitory synapse function, such as the postsynaptic scaffolding protein gephyrin and the RhoGEF collybistin. However, the majority of known interactors either bind to the GlyR α1 and β subunits, or the binding partner in the GlyR complex is unknown. Several potential GlyR interactors are not found at inhibitory synapses and/or have no clear functional role. Moreover, other GlyR interactors are <i>secondary interactors</i> that bind indirectly, for example, via gephyrin. In this review, we provide a critical evaluation of known GlyR interacting proteins and methodological limitations to date. We also provide a road map for the use of innovative and emerging interaction proteomic techniques that will unlock the GlyR interactome. With the emergence of disease-associated missense mutations in the α1, α2 and β subunit intracellular domains in startle disease and NDDs, understanding the identity and roles of GlyR accessory proteins is vital in understanding GlyR function and dysfunction in health and disease.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Careful Examination of a Novel Azobenzene Paroxetine Derivative and Its Interactions With Biogenic Amine Transporters","authors":"Dominik Dreier,&nbsp;Oliver John V. Belleza,&nbsp;Katharina Schlögl,&nbsp;Stefanie Kickinger,&nbsp;Eva Hellsberg,&nbsp;Felix P. Mayer,&nbsp;Walter Sandtner,&nbsp;Philipp Mikšovsky,&nbsp;Matthias Schittmayer,&nbsp;Yuntao Hu,&nbsp;Kathrin Jäntsch,&nbsp;Marion Holy,&nbsp;Gerhard F. Ecker,&nbsp;Harald H. Sitte,&nbsp;Marko D. Mihovilovic","doi":"10.1111/jnc.70068","DOIUrl":"https://doi.org/10.1111/jnc.70068","url":null,"abstract":"<p>The serotonin transporter (SERT) belongs to the family of neurotransmitter sodium symporters (NSS), together with other neurotransmitter transporters for norepinephrine, dopamine, glycine, and GABA. The main physiological role of SERT is the retrieval of previously released serotonin from the synaptic cleft. Thereby, SERT plays an important role in regulating the extracellular serotonin concentration and maintaining serotonergic neurotransmission. This process can be influenced by molecules acting as serotonin uptake inhibitors, like paroxetine. Here, we report the development of a novel photoswitchable paroxetine derivative and its pharmacological interaction profile with SERT as a tool compound for the light-induced control of SERT. Based on the azo-extension strategy, the photoswitchable moiety was formed at the former position of the fluoro substituent in paroxetine. The resulting azo-paroxetine (<b>9</b>) was easily and reversibly switched between active (<i>Z</i>) and inactive (<i>E</i>) configurations and remained stable between these configurations: serotonin uptake was inhibited more than 12 times more potently by the active (<i>Z</i>)-configuration having a sub μM IC₅₀ value. This was supported by electrophysiological patch-clamp recordings in the whole-cell configuration and docking studies. No significant toxic impact of azo-paroxetine (<b>9</b>) and no off-target activity at the norepinephrine transporter (NET), human GABA transporter subtypes 1 and 3, and rat GAT1 were observed. Our results demonstrate that the activity of SERT can be reversibly manipulated by the optopharmacological agent azo-paroxetine (<b>9</b>). This compound can thus be applied as a tool for the selective manipulation of SERT in central or peripheral investigations, further benefiting from its low probability for compound-related off-target effects.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of cGMP-Signalling Rescues Retinal Ganglion Cells From Axotomy-Induced Degeneration","authors":"Katia Ihadadene,&nbsp;Azdah Hamed A Fallatah,&nbsp;Yu Zhu,&nbsp;Arianna Tolone,&nbsp;François Paquet-Durand","doi":"10.1111/jnc.70072","DOIUrl":"https://doi.org/10.1111/jnc.70072","url":null,"abstract":"<p>The axons of retinal ganglion cells (RGCs) form the optic nerve, which relays visual information to the brain. RGC degeneration is the root cause of a variety of blinding diseases linked to optic nerve damage, including glaucoma, the second leading cause of blindness worldwide. The underlying cellular mechanisms of RGC degeneration are largely unclear; yet, they have been connected to excessive production of the signalling molecule nitric oxide (NO) by nitric oxide synthase (NOS). NO activates soluble guanylate cyclase (sGC), which subsequently produces the second messenger cyclic guanosine monophosphate (cGMP). This, in turn, activates protein kinase G (PKG), which can phosphorylate downstream protein targets. To study the role of NO/cGMP/PKG signalling in RGC degeneration, we used organotypic retinal explant cultures in which the optic nerve had been severed. We assessed the activity of NOS, RGC death and survival at different times after optic nerve transection. While NOS activity was high right after optic nerve transection, significant RGC loss occurred with a 24–48-h delay. We then treated retinal explants with inhibitors selectively targeting either NOS, sGC, PKG, or Kv1.3 and Kv1.6 voltage-gated potassium channels. While all four treatments reduced RGC death, the PKG inhibitor CN238 and the Kv-channel blocker Margatoxin (MrgX) showed the most pronounced rescue effects. Our results confirm an involvement of NO/cGMP/PKG signalling in RGC degeneration, highlight the potential of PKG and Kv1-channel targeting drugs for treatment development, and further suggest organotypic retinal explant cultures as a useful model for investigations into optic nerve damage.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Double-Edged Sword: The Complex Function of Enteric Glial Cells in Neurodegenerative Diseases","authors":"Ingrid Prata Mendonça,&nbsp;Christina Alves Peixoto","doi":"10.1111/jnc.70069","DOIUrl":"https://doi.org/10.1111/jnc.70069","url":null,"abstract":"<p>Over the past two decades, a growing number of studies have been conducted on the role of bidirectional communication through the gut–brain axis in the development of neurodegenerative diseases. These studies were driven by the curious fact that all of these diseases present varying degrees of intestinal involvement included in their wide range of symptoms. A population of cells belonging to the ENS, called enteric glial cells (EGCs), appears to actively participate in this communication between the intestine and the brain, but acting in a dualistic manner, sometimes in reactive gliosis releasing inflammatory mediators, sometimes promoting homeostasis and resilience in the face of inflammatory injuries. To date, the intracellular mechanisms that define the transcriptional profile expressed in EGCs in each situation have not yet been elucidated. This review proposes a discussion on: (1) the complex role of distinct phenotypes of enteric glial cells involved in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS); and (2) innovative strategies such as IDO/TDO inhibitors, Brazil nuts, caffeic acid, polyphenols, among others, that act on EGCs and have the potential to treat neurodegenerative diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}