ACS Chemical Neuroscience最新文献

{"title":"Structure–Activity Relationship Studies of l-Ascorbic Acid: Exploring Structural Requirements for the Potentiation of Human α9α10 Receptors","authors":"Jordan Oman,&nbsp;Pooja Sapkota,&nbsp;Seyedeh Melika Akaberi,&nbsp;Sameena Mateen,&nbsp;Marvin Schulte,&nbsp;Srinath Pashikanti","doi":"10.1021/acschemneuro.6c00107","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00107","url":null,"abstract":"<p><span>l</span>-ascorbic acid (AA), Vitamin-C,is a reductonethat actsas a free radical scavenger, antioxidant, and critical cofactor inmany biological pathways. Previously, AA was identified as a positiveallosteric modulator (PAM) of α9α10 nicotinic acetylcholinereceptors (nAChRs). Enhanced activation of these receptors on outerhair cells (OHC) in the cochlea may protect from noise-induced hearingloss. Structural analogs of AA were synthesized in this study to identifypharmacophoric features of AA important to its function as an α9α10nAChR PAM. Analogs were evaluated for both their antioxidant activityand their potency and efficacy in modulating acetylcholine-inducedresponses on α9α10 receptors expressed in <em>Xenopus</em> oocytes. Analogs with modified polyhydroxygroups were synthesized to assess the electron density distributionof AA analogs. Two compounds (<strong>12</strong> and <strong>25</strong>)were identified that display increased potency (half maximal effectiveconcentration, EC₅₀) for potentiation, with less efficacy(maximal efficacy, <em>E</em>_max), compared toAA. One of the active compounds was modified at the C3-hydroxyl group.Removal of the double bond between carbon 2 and 3 eliminated PAM activity.Compound <strong>12</strong> displayed the greatest potency (198.1 nM)compared to 1.80 mM for AA (∼9000-fold increase). No correlationbetween antioxidant capacity and PAM potency was observed.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3478–3490"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305719","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":"Conditional Mutant MAPT Overexpression in Neural Organoids Elicits Robust Tau Accumulation and Pathological Transcriptomic Responses","authors":"Andrew Kjar,&nbsp;Hyosung Kim,&nbsp;Madeline R. Spetz,&nbsp;Zev Jarrett,&nbsp;Melanie Fernandez,&nbsp;Jaime Wang,&nbsp;Maria L. Russotti,&nbsp;Caroline Bodnya,&nbsp;Daniel Chavarria,&nbsp;Timothy J. Hohman,&nbsp;Vivian Gama,&nbsp;Brad Grueter,&nbsp;Jonathan M. Brunger,&nbsp;Ethan S. Lippmann","doi":"10.1021/acschemneuro.6c00376","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00376","url":null,"abstract":"<p>Modeling neurodegenerative conditions in neural organoidspresentsa potential complement to existing preclinical translation pipelines.Prior neural organoid models have generally relied on human inducedpluripotent stem cell (iPSC) lines containing disease-relevant alleles.However, this strategy limits temporal control over the initiationand progression of pathological events. In this study, we providea proof-of-concept framework showing that neurodegenerative phenotypescan be triggered by inducible expression cassettes. We developed aniPSC line harboring doxycycline-inducible mutant <em>MAPT</em>, which encodes the microtubule-associated protein tau that is implicatedin tauopathies. Induction of mutant <em>MAPT</em> via doxycyclinetreatment in differentiating neural organoids yielded accumulationof phosphorylated tau, which localized inside individual neuron somaswithin the cortical plate-like regions. Importantly, measured transcriptomicresponses to tau overexpression bore key similarities to human clinicaltranscriptomic data. Taken together, we present an approach for controllingthe initiation and progression of proteinopathy-like pathology inneural organoid systems.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3501–3516"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306043","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":"Itraconazole and Lacosamide Combination Therapy Rescues CGG Repeat Expansion Induced Neurotoxicity in Fragile X-Associated Tremor/Ataxia Syndrome","authors":"Aditi Pramod Kumari,&nbsp;Smita Karati,&nbsp;Soumalya Das,&nbsp;Shubhi Khandelwal,&nbsp;Mansee Patel,&nbsp;Amit Kumar","doi":"10.1021/acschemneuro.6c00505","DOIUrl":"10.1021/acschemneuro.6c00505","url":null,"abstract":"<p>Carriersof the <em>fragile X messenger ribonucleoprotein 1 (FMR1)</em> gene have an elevated risk of developing Fragile X-associatedtremor/ataxia syndrome (FXTAS), a progressive late-onset neurodegenerativedisorder. Expansion of CGG trinucleotide repeats within the 5’untranslated region leads to RNA-mediated toxicity and promotes theaggregation of toxic FMR1polyglycine (FMR1polyG), driving neuronaldysfunction and degeneration. Yet, effective therapies that alterdisease progression remain lacking. In this study, we evaluated adrug repurposing strategy to modulate FXTAS pathogenesis by targetingCGG repeat RNA structures using Itraconazole (ITZ), a clinically approvedantifungal, in combination with Lacosamide (LCM), an established antiepilepticdrug. The ITZ+LCM combination significantly reduced FMR1polyG aggregationand attenuated oxidative stress and cell death in an <em>in vivo</em><em>Drosophila</em> model of FXTAS. Notably,this combination also improved locomotor performance and extendedthe lifespan of model flies, with a fourfold reduction in the effectiveITZ dose. These findings were further validated at the cellular levelusing (CGG)₉₉ transfected HEK293T and COS-7 cells, whereinthe ITZ+LCM treatment suppressed FMR1polyG aggregation and correctedCGG repeat splicing defects. Biophysical studies revealed the selectiveinteraction of the drug combination with CGG-expanded RNA. These findingsidentify the ITZ+LCM combination as a promising, clinically translatabletherapeutic strategy against FXTAS to counter RNA-mediated neurotoxicity.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3562–3581"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029363","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":"In Silico Evaluation of the Effects of Temperature on the Affinity of the SV2C Ligand UCB-1A to SV2 Paralogs","authors":"Rongfeng Zou,&nbsp;Sangram Nag,&nbsp;Vasco Sousa,&nbsp;Anton Morén,&nbsp;Miklós Tóth,&nbsp;Yasir Khani,&nbsp;Elena Pedergnana,&nbsp;Anne Valade,&nbsp;Celine Vermeiren,&nbsp;Philippe Motte,&nbsp;Joël Mercier,&nbsp;Xiaoqun Zhang,&nbsp;Per Svenningsson,&nbsp;Christer Halldin,&nbsp;Andrea Varrone,&nbsp;Hans Ågren","doi":"10.1021/acschemneuro.6c00482","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00482","url":null,"abstract":"<p>Synaptic vesicle glycoproteins 2 (SV2) are integral membraneproteinsessential for neurotransmitter release and are implicated in neurologicaldisorders including epilepsy and Parkinson’s disease. In theattempt to develop a ligand selective for SV2C, and i in collaborationwith UCB Biopharma, UCB-F was identified as a potential candidate.However, the affinity of UCB-F to SV2C was found to be temperaturedependent, decreasing by about 10-fold from 4 to 37 °C. UCB-1Awas subsequently identified as SV2C ligand displaying in vitro a 100-foldselectivity for SV2C compared with SV2A. In this study, we investigatedwhether the binding of UCB-1A to SV2A and SV2C was affected by thetemperature. A combination of experimental binding assay data andmolecular dynamics (MD) simulations were used. The binding studiesrevealed that UCB-1A affinity for SV2A decreased significantly at37 °C compared with 4 °C, whereas binding to SV2C remainedlargely unchanged. MD simulations reproduced these observations, namelythat ligand RMSD values at 37 °C showed that UCB-1A binding fluctuatedmarkedly in the SV2A complex, with many trajectories exceeding the3.0 Å stability cutoff, whereas UCB-1A remained relatively well-anchoredin SV2C under the same conditions. Structural analysis showed that,while UCB-1A adopts a conserved binding pose across all paralogs stabilizedby π–π stacking and a hydrogen bond with Asp, SV2Cpossesses a unique stabilizing feature. In SV2C, Tyr298 is less exposedto the solvent and engages in a persistent hydrogen bond with Asparagine,a structural feature that reinforces pocket stability and limits temperature-induceddestabilization. This interaction is absent in SV2A, consistent withits greater temperature sensitivity. Together, these findings providea mechanistic explanation for the experimentally observed temperatureindependence of UCB-1A binding to SV2C. More broadly, the resultshighlight the importance of incorporating physiologically relevanttemperatures into SV2 ligand evaluation and demonstrate how combiningexperiments with simulations can uncover isoform-specific mechanismsof ligand recognition and stability.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3538–3544"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306019","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":"Protein Isoaspartate Repair in Amyotrophic Lateral Sclerosis: An Integrative Bioinformatic Analysis of the PCMT Gene Family","authors":"Betul Irem Yardimci,&nbsp;Ayse Gul Zurel,&nbsp;Burcu Biterge","doi":"10.1021/acschemneuro.6c00479","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00479","url":null,"abstract":"<p>Proteinhomeostasis is a fundamental determinant of neuronal survival,and its disruption contributes to the pathogenesis of amyotrophiclateral sclerosis (ALS). Protein L-isoaspartate O-methyltransferases(PCMTs) are evolutionarily conserved proteins involved in the recognitionand processing of damaged proteins through the repair of isoaspartylresidues and protein quality-control pathways; however, their potentialinvolvement in ALS remains largely unexplored. Here, we performeda comprehensive in silico characterization of the PCMT family (PCMT1,PCMTD1, and PCMTD2) by integrating structural, transcriptomic, single-cell,genetic, and protein modeling analyses. Domain analysis demonstratedthat all three proteins share a conserved PCMT domain, while predictedS-adenosylmethionine-binding motifs were identified in PCMT1 and PCMTD2but not PCMTD1, indicating evolutionary conservation with functionaldivergence. Expression profiling revealed that PCMT family genes areexpressed in ALS-relevant tissues and broadly distributed across neuronal,glial, vascular, and immune cell populations in both healthy and ALS-associatedbrain single-cell data sets. Analysis of multiple independent ALStranscriptomic cohorts identified consistent upregulation of PCMTfamily members, with PCMTD1 exhibiting the most reproducible disease-associatedexpression changes across nervous system tissues and peripheral blood.Gene set correlation analyses further revealed distinct relationshipsbetween PCMT expression and neuronal pathways, with PCMT1 showingpositive associations with axonal transport and synaptic signaling,whereas PCMTD1 and PCMTD2 displayed largely inverse correlation patterns.Rare missense variants identified in ALS patients were predicted toimpair protein function and decrease protein stability, while structuralmodeling suggested that several substitutions may disrupt conservedresidues and the local protein architecture. Collectively, these findingsidentify the PCMT family as previously underexplored candidates associatedwith ALS and provide a comprehensive framework for future mechanisticstudies investigating their roles in neuronal protein homeostasisand neurodegeneration.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3526–3537"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305760","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":"Rosmarinic Acid Inhibits β-Sheet and β-Hairpin Formation in Human Islet Amyloid Polypeptide Dimers by Stabilizing Localized C-Terminal Motifs: An REMD Study","authors":"Gang Wang,&nbsp;Xinyi Zhu,&nbsp;Ziqian Zhao,&nbsp;Xiaoxiao Wu,&nbsp;Zhenyu Qian","doi":"10.1021/acschemneuro.6c00371","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00371","url":null,"abstract":"<p>The misfolding of human islet amyloid polypeptide (hIAPP)intosoluble oligomers is a primary pathological event in type 2 diabetes,with the early dimerization process representing a critical pharmacologicaltarget. Here, we investigate the molecular mechanism by which rosmarinicacid (RA) counteracts full-length hIAPP self-association through replica-exchangemolecular dynamics. Our results show that RA drastically suppressesoverall β-sheet propensities and truncates extended, aggregation-competentβ-strands, lowering the sampled population of ordered β-hairpin-likemotifs associated with amyloidogenic hIAPP conformations. Insteadof forming compact structures, the hIAPP dimer is diverted towarddisordered, hyper-solvated topologies. This conformational remodelingis driven by spatially heterogeneous thermodynamic perturbations thatdisrupt native interpeptide contacts and transfer structured motifsinto localized turn and bend structures at the C-terminus. Energetically,RA outcompetes peptide–peptide interactions via a multimodalstrategy, preferentially anchoring to the hIAPP N-terminus throughresidues K1 and R11 while simultaneously engaging the hydrophobiccore via π–π stacking. Notably, this robust noncovalentoccupation of key amyloidogenic regions occurs spontaneously in thesimulations, offering an atomistic clue for modulating early hIAPPself-association. These structural and energetic insights clarifyhow RA interacts with transient hIAPP dimer ensembles, providing adefined biophysical framework for the rational design of amyloid inhibitors.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3491–3500"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306010","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":"Hippocampal 5-HT4/6 Receptor Antagonists Normalize Dopaminergic Dysfunction in a Rodent Model of Alzheimer’s Disease","authors":"Nicole E. Eassa,&nbsp;Stephanie M. Perez,&nbsp;Olivia J. Yang,&nbsp;Angela M. Boley,&nbsp;Daniel J. Lodge","doi":"10.1021/acschemneuro.6c00432","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00432","url":null,"abstract":"<p>Psychosis affects approximately 4 million Americans withAlzheimer’sdisease (AD), yet safe and effective pharmacological treatments remainlimited. The clinical utility of traditional antipsychotics is constrainedby an FDA black box warning regarding increased mortality in the elderly.A potential mechanistic driver for these symptoms is hyperactivityin the ventral hippocampus (vHipp), a feature common to both AD andpsychosis that has been shown in preclinical models to induce dopaminesystem dysregulation. This study explores the hypothesis that suchhippocampal dysfunction is facilitated by aberrant serotonergic signaling.Clinical and preclinical studies suggest that activation of two serotonin-responsiveG-protein-coupled receptors (GPCRs), 5-HT4R and 5-HT6R, in the hippocampuscontributes to symptoms of psychosis in AD. Although targeting thesereceptors could provide therapeutic benefits, their widespread expressionthroughout the brain raises concerns about whether systemic administrationwould yield selective effects specifically in the hippocampus. Toinvestigate this, we microinfused the selective 5-HT4 receptor antagonist(SB-204070) or the 5-HT6 receptor antagonist (PRX-07034) directlyinto the vHipp of TgWKY-AD and WKY-WT rats. Intra-vHipp blockade ofeither receptor reversed the pathological elevation of ventral tegmentalarea (VTA) dopamine neuron population activity; notably, these effectswere fully recapitulated following systemic administration. We furtherdemonstrated that 5-HT4R and 5-HT6R mRNA expressions in the vHippand nucleus accumbens (NAc) are preserved in 12-month-old TgWKY-ADrats, suggesting that these targets remain viable as the disease progresses.Together, these findings identify systemic 5-HT4R or 5-HT6R antagonismas a viable therapeutic strategy to attenuate hippocampal hyperactivityand restore dopaminergic homeostasis, offering a mechanistically groundedand potentially safer alternative for managing psychosis in AD.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3517–3525"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306059","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":"Next-Generation Psychedelic Drug Development","authors":"Lindsay P. Cameron,&nbsp;Matthew W. Johnson,&nbsp;Kevin S. Murnane,&nbsp;Mark M. Rasenick,&nbsp;Charles D. Nichols","doi":"10.1021/acschemneuro.6c00492","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00492","url":null,"abstract":"<p>Psychedelic medicine has gained rapid popularity for the treatmentof a variety of neuropsychiatric disorders, including depression,anxiety, and post-traumatic stress disorder. As novel psychedelicanalogues and treatment regimes emerge, increasing numbers of variablesare being tested. Here, we review various approaches and considerationsfor novel psychedelic therapies, including the strengths and limitationsof current assays and models. Finally, we provide guidance and considerationsfor next-generation psychedelic drug development.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3462–3477"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306063","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":"Gi Signaling Does Not Differentiate Hallucinogenic from Nonhallucinogenic 5-HT2A Receptor Agonists","authors":"Cassandra J. Hatzipantelis,&nbsp;David E. Olson","doi":"10.1021/acschemneuro.6c00743","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00743","url":null,"abstract":"<p>A recent publication by Xu et al.suggests that Gi activationfollowing5-HT2AR stimulation differentiates hallucinogenic from nonhallucinogenicagonists. Here, we reanalyze the author’s source data to demonstratethat Gi activation is less predictive of hallucinogenic potentialthan canonical effectors of 5-HT2AR signaling.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 21","pages":"3458–3461"},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305739","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":"CIRP: New Horizons for CNS Injury Biomarkers and Therapy","authors":"Na Lv,&nbsp;Hao Tian,&nbsp;Qiuyan Hao,&nbsp;Fengtang Yang,&nbsp;Hui Zhen,&nbsp;Zhonghong Cao","doi":"10.1021/acschemneuro.6c00414","DOIUrl":"https://doi.org/10.1021/acschemneuro.6c00414","url":null,"abstract":"<p>Cold-inducibleRNA-binding protein (CIRP) is a stress-responseprotein that protects cells under conditions of low temperature andother stresses. The expression of CIRP is induced by various stressors.CIRP regulates gene expression through complex, multi-layered mechanismsand plays a central role in physiological and pathological processes,including cell proliferation, apoptosis, inflammatory responses, andcircadian rhythms. In central nervous system (CNS) injuries, CIRPexhibits a dual role. Intracellular CIRP has a neuroprotective function.In contrast, when released into the extracellular space as eCIRP,it acts as a damage-associated molecular pattern (DAMP) that exacerbatesneuroinflammation. Serum levels of eCIRP are significantly elevatedin patients with CNS injuries, such as acute ischemic stroke and intracerebralhemorrhage, suggesting its potential as a biomarker for diagnosisand prognosis. Furthermore, targeting the eCIRP signaling pathwayhas shown significant therapeutic effects in various models of neurologicalinjury. Strategies include using inhibitory peptides like C23 andM3, as well as microRNA-based approaches. Here, we systematicallyreview the molecular characteristics, expression regulation, and biologicalfunctions of CIRP, with a focus on its neuroprotective role, biomarkerpotential, and therapeutic targeting in CNS injuries.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"17 20","pages":"3408–3420"},"PeriodicalIF":4.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221993","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}