Journal of Neurochemistry最新文献

{"title":"cAMP-Response Element (CRE)-Mediated Transcription by CRE-Binding Protein (CREB) Is Essential for Human Tryptophan Hydroxylase 2 Gene Expression","authors":"Yukino Nawa,&nbsp;Hanae Kaneko,&nbsp;Masaaki Tsubonoya,&nbsp;Tomoko Hiroi,&nbsp;Ryoya Takahashi,&nbsp;Tomoo Sato,&nbsp;Hiroaki Matsui","doi":"10.1111/jnc.70138","DOIUrl":"https://doi.org/10.1111/jnc.70138","url":null,"abstract":"<div>\u0000 \u0000 <p>Human tryptophan hydroxylase 2 (hTPH2), a rate-limiting enzyme in the synthesis of central serotonin, is dysregulated in various neuropsychiatric disorders. However, the regulatory mechanisms underlying <i>TPH2</i> gene expression remain unknown. Here, we aimed to analyze the cAMP signaling-mediated activation of hTPH2 promoter activity involving an inverted cAMP-response element (CRE; 5′-TAACGTCA-3′; −243/−236 relative to the transcription start site, +1). A 2-kb region of the <i>TPH2</i> gene (−1850/+141; except +10/+121, a region containing repression elements) was cloned into pGL4-Basic to construct a luciferase reporter plasmid. Promoter activity was assessed via transient transfection of RN46A cells derived from rat raphe neurons. Forskolin-induced increase in cAMP levels enhanced hTPH2 promoter activity, which was significantly suppressed by the protein kinase A (PKA) inhibitor, H-89, or CRE mutants. Gel mobility shift assays and chromatin immunoprecipitation assays confirmed the specific binding of CRE-binding protein (CREB) to CRE. hTPH2 promoter activity was decreased by endogenous CREB knockdown. Overexpression of PKAα catalytic subunit and CREB tended to increase the hTPH2 promoter activity. Furthermore, overexpression of CREB-regulated transcription co-activator 1 (CRTC1) the principal CRTC isoform in the brain, with PKAα/CREB significantly increased the hTPH2 promoter activity. In contrast, under PKAα/CRTC1 overexpression conditions, hTPH2 promoter activity was slightly decreased by the overexpression of R133A-CREB (defective for phosphorylation by PKA) and further decreased by the overexpression of R314A-CREB (defective for interaction with CRTC). Overall, our results suggest that high cAMP levels regulate the hTPH2 promoter activity mainly via PKA and its downstream effectors, such as CREB. Moreover, PKA–CRTC signaling stimulates <i>TPH2</i> gene transcription upon CREB activation.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331869","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":"The Blue Light-Responsive Lateral Pathway of the Retinohypothalamic Tract Promotes Endocannabinoid-Driven Modulation of Orexin Neurons","authors":"Nicola Forte,&nbsp;Roberta Imperatore,&nbsp;Brenda Marfella,&nbsp;Alessandro Nicois,&nbsp;Roberta Verde,&nbsp;Letizia Palomba,&nbsp;Vincenzo Di Marzo,&nbsp;Luigia Cristino","doi":"10.1111/jnc.70137","DOIUrl":"https://doi.org/10.1111/jnc.70137","url":null,"abstract":"<p>Circadian light influences brain functions in mammals. Photic non-image-forming stimuli are transduced into electrochemical signals by photosensitive retinal ganglion cells containing melanopsin, a selective blue light-responsive photopigment. The hypothalamus receives light-related information via the retinohypothalamic tract (RHT). Here, we demonstrate that, in the mouse, a lateral branch of the RHT (l-RHT) projects monosynaptically to orexin-A (OX-A) neurons in the perifornical hypothalamic area (PFH). Intravitreal injection of the anterograde tracer cholera toxin-β (CTβ) filled most of the vesicular glutamate transporter (VGluT1)/cannabinoid receptor 1 (CB1R)-positive retinal-derived inputs projecting to the OX-A neurons. Monocular injection of Fluo4-Dextran, a fluorimetric sensor of calcium mobilization, yielded fast labeling of these inputs 10 min after eye exposure to blue light, concomitantly with the enhancement of hypothalamic 2-arachidonoylglycerol (2-AG) levels, and inhibition of OX-A neuronal firing, an effect prevented by in vivo administration of the CB1R antagonist AM251. Our findings provide anatomical and functional evidence of a selective retino-hypothalamic network responsive to blue light, whose control should be suitable for therapies to counteract sleep disorders, seasonal affective disorder, or even conditions like narcolepsy or anxiety.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331992","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":"Increased Activity-Dependent Bulk Endocytosis in Huntington's Disease Results From Huntingtin Haploinsufficiency","authors":"Han C. G. Tan,&nbsp;Robyn L. McAdam,&nbsp;Andrew Morton,&nbsp;Michael A. Cousin,&nbsp;Karen J. Smillie","doi":"10.1111/jnc.70134","DOIUrl":"https://doi.org/10.1111/jnc.70134","url":null,"abstract":"<p>Huntington's disease (HD) is a life-limiting, progressive monogenic neurodegenerative disorder characterised by chorea, hypokinesis and psychosocial symptoms. HD is characterised by a variable CAG expansion in exon 1 of the <i>HTT</i> gene, which encodes the huntingtin (htt) protein. This expansion results in an extended polyglutamine tract, which is widely thought to confer a toxic gain of function on the protein that is responsible for disease progression. Most individuals with HD are heterozygous for this mutation, meaning that loss of wild-type htt function may also contribute to disease pathology. We previously identified that the recycling of synaptic vesicle proteins at the presynapse was specifically disrupted in striatal neurons from a preclinical model of HD, the <i>Htt</i>^Q140/Q140 knockin mouse. This defect was only revealed during high activity and, notably, was due to loss of wild-type htt function. The dominant endocytosis mode at the presynapse during high activity is activity-dependent bulk endocytosis (ADBE). Therefore, we determined whether dysfunction in this pathway was linked to this recycling defect. We revealed that three independent neuronal subtypes derived from <i>Htt</i>^Q140/Q140 mice displayed enhanced recruitment, but no change in the extent of ADBE via the evoked uptake of fluid phase markers. Importantly, this phenotype was due to a loss of wild-type htt function, since depletion of htt in <i>Htt</i>^+/+ neurons mimicked the defect, and removal of mutant htt from <i>Htt</i>^Q140/Q140 neurons did not correct this dysfunction. Neurons from <i>Htt</i>^Q140/+ mice, which mimic the human condition, also displayed increased activity-dependent triggering of ADBE, suggesting that htt haploinsufficiency may be responsible. This was confirmed by the inability of zinc finger proteins that selectively target mutant htt to correct this defect in <i>Htt</i>^Q140/+ neurons. Therefore, htt haploinsufficiency drives dysfunction in a key endocytosis mode that is dominant during high neuronal activity, providing a potential mechanism for circuit dysfunction that results in neurodegeneration in later life in HD.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331998","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":"Complement C3a and C5a Receptors Are Presented in Mouse Sciatic and Human Sural Nerves and Selectively Modulate the Neuronal Function of Large-Caliber Fibers in Mice","authors":"Shani Berkowitz,&nbsp;Zehavit Goldberg,&nbsp;Valery Golderman,&nbsp;Amir Dori,&nbsp;Nicola Maggio,&nbsp;Jérôme Joël Devaux,&nbsp;Efrat Shavit-Stein","doi":"10.1111/jnc.70129","DOIUrl":"https://doi.org/10.1111/jnc.70129","url":null,"abstract":"<p>Dysregulated complement activation drives peripheral inflammatory neuropathies by promoting immune attacks that exacerbate inflammation and tissue damage. Beyond immune functions, complement signaling may influence neuronal activity. To explore the role of C3a receptor (C3aR) and C5a receptor 1 (C5aR1) in peripheral nerve pathology, we examined their localization in mouse sciatic and human sural nerves and assessed their impact on nerve conduction. Immunofluorescence identified C3aR and C5aR1 in mice and human nerves. qPCR and western blot confirmed receptor expression in mouse sciatic nerves. Ex vivo electrophysiology assessed neural responses in control and treated nerves exposed to C3aR and C5aR1 agonist or agonist + antagonists. C3aR localized to the glial paranodal region of large-myelinated fibers, while C5aR1 is primarily in small unmyelinated fibers. C3aR activation enhanced large-fiber responses, reduced the refractory period, and increased excitability. The C3aR antagonist prevented these effects. In contrast, C5aR1 activation had minimal impact on conduction. These findings highlight distinct roles of C3aR and C5aR1 in peripheral nerves and suggest that Schwann cell C3aR regulates neuronal excitability. Targeting these pathways may help modulate nerve activity and inflammation in conditions like Guillain–Barré syndrome and diabetic neuropathy.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323532","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":"Low-Glucose Culture Conditions Bias Neuronal Energetics Towards Oxidative Phosphorylation","authors":"Sarpras Swain,&nbsp;David M. Roberts,&nbsp;Saad Chowdhry,&nbsp;Ryan Durbin,&nbsp;Reece Boyd,&nbsp;Juli Petereit,&nbsp;Robert Renden","doi":"10.1111/jnc.70125","DOIUrl":"https://doi.org/10.1111/jnc.70125","url":null,"abstract":"<p>Neurons are almost exclusively cultured in media containing glucose at much higher concentrations than found in the brain. To test whether these “standard” hyperglycemic culture conditions affect neuronal respiration relative to near-euglycemic conditions, we compared neuronal cultures grown with minimal glial contamination from the hippocampus and cortex of neonatal C57BL/6NCrl mice in standard commercially available media (25 mM Glucose) and in identical media with 5 mM glucose. Neuronal growth in both glucose concentrations proceeded until at least 14 days in vitro, with similar morphology and synaptogenesis. Neurons grown in high glucose were highly dependent on glycolysis as their primary source of ATP, measured using ATP luminescence and cellular respirometry assays. In contrast, neurons grown in 5 mM glucose showed a more balanced dependence on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), greater reserve mitochondrial respiration capacity, and increased mitochondrial population relative to standard media. Our results show that neurons cultured in artificially high glucose-containing media preferentially use glycolysis, opposite to what is known for neurons in vivo as the primary pathway for ATP maintenance. Changes in gene and protein expression levels corroborate these changes in function and additionally suggest that high glucose culture media increases neuronal inflammation. We suggest using neuronal culture systems in 5 mM glucose to better represent physiologically relevant neuronal respiration.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315306","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":"Correlation Analysis Between High-Density Lipoprotein Cholesterol-Carried microRNA-28-5p and Acute Ischemic Stroke","authors":"Xiyue Zhang","doi":"10.1111/jnc.70119","DOIUrl":"https://doi.org/10.1111/jnc.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>This paper aimed to disclose the correlation of high-density lipoprotein cholesterol (HDL-C)-carried microRNA-28-5p (miR-28-5p) with acute ischemic stroke (AIS). This study retrospectively included 216 first-diagnosed AIS patients (study subjects) and 102 healthy people (controls). Clinical data, serum total cholesterol (TC), triglycerides (TG), glucose, homocysteine (Hcy), HDL-C, low-DL-C (LDL-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and fasting serum samples were collected. Serum miR-28-5p levels and disease severity were assessed by RT-qPCR and National Institutes of Health Stroke Scale (NIHSS). The diagnostic efficacy of miR-28-5p and Hcy for AIS and disease severity was evaluated using ROC curves. miR-28-5p was upregulated in AIS patients, positively correlated with HDL-C (<i>p</i> &lt; 0.001, <i>r</i> = 0.848), and negatively correlated with TC (<i>p</i> &lt; 0.001, <i>r</i> = 0.673). HDL-C-carried miR-28-5p was an independent influencing factor for AIS (<i>p</i> = 0.027, OR = 1.294, 95% CI = 1.030–1.626) and helped diagnose AIS (AUC = 0.938, 95% CI = 0.912–0.963). miR-28-5p was positively correlated with NIHSS scores (<i>p</i> &lt; 0.001, <i>r</i> = 0.777) in AIS patients, and provided diagnostic value for AIS (positive predictive value [PPV] = 96.907%, negative predictive value [NPV] = 77.419%) and AIS severity (PPV = 95.200%, NPV = 75.824%). PPV &gt; 95% and NPV &lt; 90% suggested that miR-28-5p offered auxiliary diagnostic value for AIS and its severity, with limited diagnostic accuracy, and there might be a relatively high risk of missed diagnosis. The combination of miR-28-5p and Hcy improved the diagnostic value of miR-28-5p alone for AIS and its severity. Collectively, HDL-C-carried miR-28-5p is highly expressed in AIS patients and positively correlated with NIHSS score. It is an independent influencing factor for AIS and may assist in diagnosing AIS and its severity. Additionally, miR-28-5p combined with Hcy can increase the diagnostic value of miR-28-5p single detection for AIS and its severity.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315224","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":"The Regulatory Roles of REST in the Synaptic Development, Function and Related Neurological Disorders","authors":"Chong Teik Lim,&nbsp;Cheng Wei Lim,&nbsp;Tan Huang,&nbsp;Elysha Nur Ismail,&nbsp;Parham Reisi,&nbsp;Pike See Cheah,&nbsp;King Hwa Ling","doi":"10.1111/jnc.70132","DOIUrl":"https://doi.org/10.1111/jnc.70132","url":null,"abstract":"<p>The synaptic system is the core of the nervous system, coordinating neural communication. Synaptic dysfunctions, including deficits in synaptogenesis, neurotransmission and plasticity, underlie various neurological diseases. Repressor element-1 silencing transcription factor (REST), an epigenetic transcription factor, plays a crucial role in neurodevelopment and neuroprotection by fine-tuning the expression of neuronal genes. REST binds to the RE-1 motif on target genes and recruits cofactors to exert transcriptional regulation. Dysregulation of REST, affecting thousands of downstream neuronal genes, is characteristic of neurological diseases with synaptic dysfunctions, including Huntington's disease, Alzheimer's disease, epilepsy, cerebral ischaemia, bipolar disorder and Kleefstra syndrome. Research on REST-targeted synaptic genes has been ongoing since 1993, using various fundamental and disease neuronal models. However, there has been no comprehensive review to consolidate the scattered knowledge of the regulatory role of REST in the synaptic system. Therefore, we reviewed and identified a list of REST-targeted and -regulated synaptic genes to address this gap. We found that REST plays significant roles in synapse development and function, particularly in the synaptic vesicle cycle, chemical neurotransmission systems and homeostasis of synaptic plasticity. Importantly, approaches to restore REST level in various neurological diseases have successfully rescued REST-targeted synaptic gene expression and ameliorated their synaptic and neuronal functions. This review serves as a foundation for future research on REST and neurological diseases. It aims to delineate the regulatory role of REST in the synaptic system and explore the potential of targeting REST restoration to improve synaptic functions in various neurological 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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315367","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":"Correction to ‘Inhibition of cGMP-Signalling Rescues Retinal Ganglion Cells From Axotomy-Induced Degeneration’","authors":"","doi":"10.1111/jnc.70127","DOIUrl":"https://doi.org/10.1111/jnc.70127","url":null,"abstract":"<p>Ihadadene, K., Fallatah, A.H.A., Zhu, Y., Tolone, A. and Paquet-Durand, F. (2025), Inhibition of cGMP-Signalling Rescues Retinal Ganglion Cells From Axotomy-Induced Degeneration. <i>J Neurochem, 169</i>: e70072. https://doi.org/10.1111/jnc.70072</p><p>In the paper by Ihadadene, Fallatah et al. (2025), some errors appeared.</p><p>In Section 2.7, the text, ‘using the two-stage step up method of Benjamini, Krieger and Yekutieli’ should have read ‘using the two-stage step-up method of Benjamini, Krieger and Yekutieli’.</p><p>In Section 3.2, citations to Figure 3 should have been included. The correct text appears below:</p><p>The results obtained indicated elevated NOS activity (NOS activity-positive GCL cells: 4173 ± 1183 SD) already at the earliest time points after optic nerve transection (Figure 3a,b). Citrulline-positive cells were almost undetectable (Figure 3c,d), while cell death in the retinal GCL, as assessed by the TUNEL assay, was initially very low (TUNEL-positive cells: 16.3 ± 14.2 SD) (Figure 3g,h). At the earliest post-axotomy time points, the normal, full complement of RBPMS-positive cells was detected, averaging 4801 (±225 SD) cells/mm² (Figure 3e,f), a value that agrees well with previous data for the mouse retina (Dräger and Olsen 1981).</p><p>In Section 3.2, the phrase ‘citruslline- and TUNEL-positive cells’ should read ‘citrulline- and TUNEL-positive cells’.</p><p>In Section 3.3, a citation to Figure 4 should have been added. The correct text appears below:</p><p>Quantification of calretinin-positive cells within the GCL revealed a significant decrease after 24 h treatment with ODQ and CN238 (p: 0.0018, 0.0488, respectively), while 7-NI and MrgX had no effect (p: 0.4167, 0.7914, respectively) (Figure 4e,f).</p><p>For Figure 5, the legend should have included the text ‘Scale bar: 50 μm’.</p><p>In Section 3.4: In the last sentence of the paragraph, the citation of Figure 6h is missing. The correct text should be ‘Figure 6g,h,i’.</p><p>In Section 6, Sentence 2, a full stop is missing before the sentence: ‘For RGCs, the destructive role of excessive NO-signalling is also rather clear…’.</p><p>The ORCID IDs for the co-authors should have been added:</p><p>Katia Ihadadene: https://orcid.org/0009-0007-3905-4048</p><p>Azdah hamed A Fallatah: https://orcid.org/0009-0007-2720-5021</p><p>Francois Paquet-Durand: https://orcid.org/0000-0001-7355-5742</p><p>Yu Zhu: https://orcid.org/0000-0003-2727-1356</p><p>We apologise for these mistakes, which were caused by inadvertent omission in the final stage of manuscript preparation.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315366","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":"Bioanalytical Considerations for Biomarkers of Parkinson's Disease","authors":"Aric Huang,&nbsp;Robert S. Foti,&nbsp;C. Geeth Gunawardana,&nbsp;Honglue Shen,&nbsp;Yingwen Xiao","doi":"10.1111/jnc.70131","DOIUrl":"https://doi.org/10.1111/jnc.70131","url":null,"abstract":"<p>Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by damage to dopaminergic cells. Early detection of PD is challenging due to the late appearance of clinical symptoms. Therefore, reliable biomarkers are needed to help identify subjects at risk and allow for early intervention, as well as for better monitoring of disease progression and response to therapy. α-Synuclein (α-syn) has emerged as a potential biomarker for PD, along with other biomarkers such as cytokines, amyloid β42, tau protein, and neurofilament light chain. Despite the abundance of biomarker discovery research, comparative studies and biomarker validation have been difficult due to the lack of large longitudinal studies and the corresponding bioanalytical challenges, which limit accurate biomarker measurements and identification. Key bioanalytical challenges in biomarker identification include the need for very sensitive assays with low limits of detection and quantitation, low sample volumes, potential matrix effects, significant amounts of pre-analytical sample processing, and the need to avoid interpretive bias. Various bioanalytical platforms, such as ELISA, MSD, Luminex, Simoa, and mass spectrometry, are used for protein quantification, each with their own advantages and limitations. An α-synuclein seed amplification assay (αSyn-SAA) has shown promise in detecting α-syn aggregates, but standardization and optimization are necessary. Overall, the identification of robust biomarkers for PD requires collaboration, standardization, and the development of sensitive and specific assays.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309019","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":"Extensive Clinical Flow Cytometric Lymphocyte Phenotyping in Myasthenia Gravis: A Single-Center Study","authors":"Hannes Lindahl,&nbsp;Malin Petersson,&nbsp;Sara Lind Enoksson,&nbsp;Fredrik Piehl,&nbsp;Susanna Brauner","doi":"10.1111/jnc.70126","DOIUrl":"https://doi.org/10.1111/jnc.70126","url":null,"abstract":"<p>Myasthenia gravis (MG) is an autoimmune neurological disease characterized by potentially life-threatening muscular fatiguability. Symptoms are directly linked to autoantibodies targeting postsynaptic receptors of the neuromuscular junction. However, the underlying immunopathogenesis remains to be elucidated. This single-center study aimed to characterize peripheral blood lymphocytes in MG patients and to identify prognostic biomarkers. We retrospectively reanalyzed clinical flow cytometric data on blood B and T cells from 76 incident MG cases, comparing them to healthy individuals of relevant age range. Clinical data was collected from the Swedish MG registry and used for outcome analyses. Flow cytometry analyses were based on standardized panels established by the Human Immunology Project Consortium and included a 10-color T cell panel focused on memory, polarization, and activation states and an 8-color B cell panel that includes memory phenotypes, transitional B cells and plasmablasts. Groupwise comparisons, survival curves, and regression models adjusting for potential confounders were used to assess potential predictors of the primary outcome, minimal disease manifestation within one year. Untreated MG patients had higher frequencies of cluster of differentiation 4 (CD4) T cell frequencies compared to healthy individuals of approximately the same age (median 75% vs. 63% in age range 40–59 years and 65% in 60–81 years). High CD4 T cell frequencies (&gt; 75% of total T cells) were associated with lower probability of minimal disease manifestation within one year (35% vs. 67%; log rank <i>p</i> = 0.032). In a multivariable Cox regression model assessing time to minimal disease manifestation, CD4 T cell frequency was an independent risk factor (<i>p</i> = 0.0014). In conclusion, MG patients appear to display an altered CD4 T cell phenotype and frequency of CD4 T cells is a potential prognostic biomarker.\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 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300134","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}