Current Neuropharmacology最新文献

{"title":"Development and Validation of a Nomogram to Predict Minimal Symptom Expression in AChR+ gMG Patients Undergoing Efgartigimod Therapy.","authors":"Chi Ma, Nan Kang, Ying Zhu, Tianying Ma, Jingyi Shen, Benqiao Wang, Ruixia Zhu","doi":"10.2174/011570159X499275260731080332","DOIUrl":"https://doi.org/10.2174/011570159X499275260731080332","url":null,"abstract":"<p><strong>Background: </strong>Efgartigimod has emerged as an effective treatment option for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG). This study aimed to develop and validate a predictive nomogram to evaluate the achievement of Minimal Symptom Expression (MSE) in AChR+ gMG patients following efgartigimod treatment.</p><p><strong>Methods: </strong>We retrospectively reviewed 119 patients with AChR+ gMG who received at least one cycle of efgartigimod and had ≥ 12 weeks of follow-up. Clinical response was defined as MSE, referring to an MG-ADL score of 0 or 1 within 4 weeks of treatment initiation and sustained for ≥ 4 consecutive weeks. Independent predictors of MSE were identified using multivariable logistic regression and incorporated into a nomogram. Model performance was assessed by discrimination (AUC-ROC) and calibration, with internal validation performed using bootstrap resampling.</p><p><strong>Results: </strong>The MSE responder rate was 37.0%. New-onset MG (OR=2.691, p=0.031), thymoma-associated MG (TAMG) (OR=0.209, p=0.027), baseline QMG score (OR=0.888, p=0.007), and the reduction in IgG levels after one treatment cycle (ΔIgG) (OR=1.168, p=0.040) were independently associated with the clinical response. The nomogram demonstrated moderate discrimination, with a bootstrap-corrected AUC of 0.744 (95% CI: 0.732-0.771), indicating stable performance after internal validation.</p><p><strong>Discussion: </strong>The nomogram indicates that new-onset MG and ΔIgG are associated with a higher probability of achieving MSE, while TAMG and a higher baseline QMG score are linked to poorer outcomes. These findings further support the potential value of early intervention and dynamic IgG monitoring in guiding individualized treatment strategies.</p><p><strong>Conclusion: </strong>By integrating new-onset MG, TAMG, baseline QMG score, and ΔIgG, this nomogram provides an individualized prediction of MSE in AChR+ gMG patients treated with efgartigimod, offering a practical clinical tool to help tailor treatment strategies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808404","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}

{"title":"Neuroprotective Natural Products: Extraction and Separation, Structural Identification, Biological Evaluation, Structure-activity Relationship, and Mechanism.","authors":"Qin-Ge Ma, Rong-Rui Wei, Wen-Min Liu, Chun-Su Yuan, Jian-Bo Yang, De-Wu Zhang","doi":"10.2174/011570159X532787260807102215","DOIUrl":"https://doi.org/10.2174/011570159X532787260807102215","url":null,"abstract":"","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807922","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}

{"title":"Metformin in Neurodegenerative Diseases: Mechanisms and Therapeutic Implications.","authors":"Aveline P Langmead, Breauna A Keane, Jive A Jacob, Kota V Ramana","doi":"10.2174/011570159X476604260704180015","DOIUrl":"https://doi.org/10.2174/011570159X476604260704180015","url":null,"abstract":"<p><p>As the global burden of neurodegenerative disorders continues to rise with aging populations, there is growing interest in identifying widely available drugs that can be repurposed to target shared metabolic and inflammatory mechanisms underlying these conditions. Increasing evidence suggests that metabolic dysfunction, mitochondrial impairment, and chronic neuroinflammation play central roles in the pathogenesis of neurodegeneration, demonstrating the need for therapeutics that can modulate these interconnected pathways. Metformin has served as the gold standard for the management of type 2 diabetes for 7 decades. It offers a superior safety profile, established metabolic advantages, and affordability. Recent studies suggest that, in addition to its antihyperglycemic actions, it could also be repurposed to treat several inflammatory complications and infectious diseases. Further, recent preclinical and clinical studies suggest that, by regulating AMPK, mTOR, and mitochondrial function, metformin could also control the initiation and progression of neurodegenerative diseases. Several studies also indicate that metformin suppresses neuroinflammation by inhibiting the NF-κB signaling pathway and the NLRP3 inflammasome, thereby improving insulin signaling and metabolic homeostasis. This review integrates metabolic, inflammatory, and mitochondrial mechanisms to present a unified mechanistic framework to explain how metformin may modulate the onset and progression of neurodegeneration. Specifically, we discuss recent studies showing the therapeutic significance of metformin in Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Moreover, this review highlights metformin as a potential therapeutic candidate for future development in neurodegenerative diseases.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807935","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}

{"title":"Effect of Adipose-derived Stem Cell Exosomes in Alleviating Experimental Autoimmune Encephalomyelitis by Reducing the Th17-related Immune Response in the Central Nervous System.","authors":"Do-Won Ham, Cho-Yeon Park, Seung-Hwan Seo, Ji-Eun Lee, Eun-Hye Lee, Sun-Young Kim, Eun-Hee Shin","doi":"10.2174/011570159X464294260728104444","DOIUrl":"https://doi.org/10.2174/011570159X464294260728104444","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Multiple Sclerosis (MS) is an immune-mediated neuroinflammatory disease of the central nervous system. Its progression is driven by persistent inflammation and demyelination, which are largely exacerbated by an imbalance between pathogenic Th17 lymphocytes and immunosuppressive regulatory T cells (Tregs). Exosomes derived from Adipose-Derived Stem Cells (ADSC-EXOs) have emerged as promising therapeutic agents because of their robust immunomodulatory properties and ability to cross the Blood-Brain Barrier (BBB). However, their capacity to modulate Th17/Treg dynamics within the CNS and to exert sustained immunoregulatory effects has not been fully elucidated. This study investigated the efficacy of ADSC-EXOs in ameliorating Experimental Autoimmune Encephalomyelitis (EAE), and examined the underlying mechanisms governing their influence on the Th17/Treg balance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EAE was induced in C57BL/6 mice through immunization using the MOG₃₅-₅₅ peptide antigen, followed by four intravenous administrations of ADSC-EXOs at 3-day intervals. Exosome identity and purity were confirmed using nanoparticle tracking analysis, transmission electron microscopy, and western blotting for exosomal markers. Clinical scores and body weights were monitored for 42 days. CNS histopathology, microglial activation, and the distribution of Th17 (IL-17A⁺/CD4⁺) and Treg (Foxp3⁺/CD4⁺) cells were evaluated using immunostaining, flow cytometry, and qRT-PCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;ADSC-EXO-treated mice exhibited significantly reduced clinical scores compared to untreated EAE mice (CS: 2.3 vs. 3.0 at day 42), along with decreased demyelination and suppressed microglial activation. Immunofluorescence revealed a marked reduction in Th17 cells in both the brain (82.0 vs. 14.7 cells/mm²) and spinal cord (68.0 vs. 36.1 cells/mm²) ADSC-EXO-treated mice compared to untreated EAE controls. This was accompanied by a reciprocal increase in Treg cells in the treated cohort (brain: 42.6 vs. 14.6 cells/mm²; spinal cord: 40.0 vs. 14.3 cells/mm²). The upregulation of anti-inflammatory markers (Foxp3, CTLA-4, and TGF-β) further confirmed restoration of the Th17/Treg balance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;ADSC-EXOs ameliorated EAE pathology by selectively modulating CNS immune responses. Rather than broadly suppressing inflammation, ADSC-EXO treatment reshaped the immune microenvironment by restoring the dynamic balance between pathogenic Th17 cells and regulatory T cells. Notably, ADSC-EXOs suppressed microglial activation without overt effects on astrocytes, suggesting a targeted immunomodulatory mechanism within the inflamed CNS. Furthermore, the persistence of immune cell rebalancing beyond the period of exosome retention suggests a prolonged immunoregulatory effect. This may reflect a stable immunoregulatory state maintaining Treg function independently of continued exosome presence, although the precise mechanisms remain un","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808386","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}

{"title":"From Self-Assembly to Survival: Neuropeptide Precursor Biology in Neuroprotection.","authors":"Camille Rabesahala de Meritens, V L Katanaev, Mikhail Kryuchkov","doi":"10.2174/011570159X476180260713054521","DOIUrl":"https://doi.org/10.2174/011570159X476180260713054521","url":null,"abstract":"<p><p>Neuropeptides (NPs) are central regulators of neuronal communication, homeostasis, and adaptive responses to stress. Beyond their well-established roles in modulating behaviour, metabolism, and circadian rhythms, NPs exert potent neuroprotective effects in acute neurological disorders, including ischemic stroke, traumatic brain injury, epilepsy, and neuroinflammatory insults. These protective actions encompass suppression of neuroinflammation, attenuation of excitotoxicity, preservation of mitochondrial integrity, and promotion of neuronal survival and plasticity. However, the efficacy and spatial precision of NP signalling critically depend on the biology of their precursors (NPPs), which are increasingly recognised as active regulators rather than inert biosynthetic intermediates. In this review, we synthesise emerging evidence that NPPs self-assemble and condense within dense-core secretory vesicles through tightly regulated, liquid-liquid phase separation (LLPS)-like mechanisms governed by pH, Ca2+, lipid composition, and intrinsic sequence features. This regulated condensation facilitates selective cargo sorting, efficient proteolytic processing, and controlled release of mature NPs. Importantly, we contrast this physiological, reversible self-assembly with the pathological protein aggregation characteristic of neurodegenerative disease, highlighting how dysregulation of NPP condensation and processing may contribute to impaired neuroprotective signalling in acute and chronic neurological disorders. We further review how key neuroprotective NPs, including α-melanocyte-stimulating hormone (α-MSH), galanin, orexins, neuropeptide Y (NPY), neuropeptide S (NPS), nesfatin-1, and adrenocorticotropic hormone (ACTH)-derived peptides, mitigate acute neuronal injury by modulating microglial activation, inflammatory cytokine production, excitatory-inhibitory balance, and apoptotic pathways. Finally, we discuss therapeutic strategies that leverage NPP and NP biology, including stabilisation of precursor processing, modulation of vesicular environments, and development of peptide analogues and peptidomimetics. By reframing NPPs as upstream determinants of neuroprotective peptide availability, this review highlights new conceptual and translational avenues for innovative neuroprotective therapies in acute neurological disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808341","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}

{"title":"Retina-Brain Axis in Postoperative Delirium: Mechanistic Links, Single-Cell/Omics Evidence, and Translational Opportunities.","authors":"Weibin Huang, Mengquan Tan, Muxuan Fang, Xinran He, Huixian Zhou, Xiaowei Wei, Qin Xie, Shengtao Liu, Tong Wang, Siyuan Song, Yaling Dai","doi":"10.2174/011570159X493268260722105849","DOIUrl":"https://doi.org/10.2174/011570159X493268260722105849","url":null,"abstract":"<p><p>Postoperative Delirium (POD) is a common, mechanistically heterogeneous neuropsychiatric syndrome characterized by acute neuroinflammation and neurovascular dysfunction. Despite its clinical significance, the lack of accessible biomarkers to monitor Central Nervous System (CNS) vulnerability remains a major barrier to effective risk stratification. The retina, as an embryological extension of the CNS, shares highly conserved neurovascular and immune architectures with the brain, including blood-barrier parallels and glial-mediated neurovascular coupling. This biological continuity suggests that retinal structure and microvasculature can serve as a noninvasive \"proxy\" for cerebral health. Recent single-cell and multiomic atlases have identified overlapping cellular programs in the retina and brain involving complement activation, endothelial activation (e.g., ICAM1, MMP9), and innate immune reprogramming. Furthermore, retinal circadian pathways via intrinsically photosensitive retinal ganglion cells (ipRGCs) provide a direct link to the sleep-wake instability observed in POD. Emerging clinical data demonstrate that preexisting Retinal Nerve Fibre Layer (RNFL) thinning is associated with increased delirium risk, reflecting a lower \"neural reserve\" to withstand perioperative stress. Handheld Optical Coherence Tomography (OCT) studies further confirm the feasibility of bedside retinal imaging in frail surgical populations, such as hip fracture patients. This review synthesizes these strands into an integrated \"Retina-Brain Axis\" model. We argue that combining retinal phenotyping with EEG and omics data is not only scientifically justified but also clinically necessary to transition from generic care to precision-based, mechanistically guided POD prevention and monitoring.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789308","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}

{"title":"Dysfunctional Crosstalk in Ischemic Stroke: Exploring Network Failure and Emerging Communication Pathways.","authors":"Song Wang, Yitong Du, Sichen Wang, Yuhan Sun, Jingyi Yao, Dan Xie","doi":"10.2174/011570159X460709260721113119","DOIUrl":"https://doi.org/10.2174/011570159X460709260721113119","url":null,"abstract":"<p><p>Ischemic stroke damages complex, interconnected communication networks in addition to causing the destructive collapse of cells. All elements of the neurovascular unit (NVU), including the often disregarded glycocalyx and invading peripheral immune cells, interact dynamically and frequently contradict one another in their pathophysiological processes, which extend beyond neurons. This paper reviews developments in intercellular communication pathways that regulate brain injury and repair after cerebral ischemia. The intricate signaling networks among neurons, astrocytes, microglia, oligodendrocytes, endothelial cells, pericytes, and lymphocytes were comprehensively analyzed. This review goes beyond conventional viewpoints to highlight major findings, ongoing debates, and critical research gaps associated with each interaction. This study investigated the dual nature of glial responses by analyzing diverse activation states of glial cells, the mechanisms underlying blood-brain barrier (BBB) disruption, including glycocalyx degradation, and the complex immunoregulatory roles of lymphocyte subsets, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and γδ T cells. In addition to classical soluble factor signaling, emerging communication mechanisms, including extracellular vesicles (EVs), tunneling nanotubes (TNTs), and migrasomes, were investigated, and these mechanisms may be involved in ischemic pathophysiology. Contradictory data and mechanistic evidence were assessed for every communication pathway; knowledge gaps were identified, and specific experiments were proposed to resolve these uncertainties. Finally, these observations were integrated into a discussion of advanced therapeutic approaches based on network modulation. This review offers a potential framework for discovering new system-based treatment targets targeted at rewiring harmful crosstalk and fostering strong neurological recovery by characterizing ischemic stroke as a progressive failure of intercellular communication.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705721","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}

{"title":"Exploratory Longitudinal Pilot Study of Proteomic and Metabolomic Profiling Suggests a Hypothesized PIAS4-NF-κB-Stearic Acid Model in Atypical Depression.","authors":"Weidi Wang, Yueyang Li, Rubai Zhou, Lei Ding, Guan Ning Lin, Peijun Ju, Xiaowen Hu, Chunling Wan, Daihui Peng","doi":"10.2174/011570159X480041260722224459","DOIUrl":"https://doi.org/10.2174/011570159X480041260722224459","url":null,"abstract":"<p><strong>Objective: </strong>Major Depressive Disorder (MDD) with atypical features, briefly named Atypical Depression (AFD), exhibits affective instability and metabolic-immune abnormalities, yet objective biomarkers remain lacking. This exploratory longitudinal pilot study aimed to evaluate whether plasma proteomic and metabolomic profiling could nominate candidate immune-metabolic signatures associated with AFD.</p><p><strong>Methods: </strong>This longitudinal pilot study included five female AFD patients assessed at baseline, 3 months, and 1 year, and five healthy female controls assessed at baseline. Plasma samples were collected at predefined time points for SomaScan®-based proteomic profiling and UHPLC-QTOF-MS-based untargeted metabolomic profiling. Ensemble Feature Selection (EFS), co-expression network analysis (WGCNA), and multi-omics integration (O2PLS, correlation) were applied to identify immuno-metabolic signatures associated with affective instability.</p><p><strong>Results: </strong>EFS nominated candidate proteins (e.g., IFN-λ1, PIAS4, CD63) and metabolites (e.g., glutamic acid, uric acid, stearic acid) involved in immune response and oxidative stress as prioritized features in AFD. WGCNA clustered 19 proteomic modules, with at least eight enriched for immune/inflammatory pathways. The salmon module, associated with innate immunity, showed a nominal inverse Pearson correlation with stearic acid (r = -0.55, p = 0.01). Cross-omics analysis further suggested shared proteomic-metabolomic covariance, and focused analysis showed an inverse PIAS4-stearic acid pattern in the joint latent space.</p><p><strong>Discussion: </strong>The findings suggest that AFD may involve dynamic immune-metabolic alterations. The longitudinal design indicates that these molecular changes may evolve over time rather than represent fixed abnormalities, potentially reflecting ongoing interactions between inflammatory processes and metabolic regulation. Notably, the exploratory inverse relationship between stearic acid and a PIAS4-centered immune module points to a potential link between lipid metabolism and innate immune activity. Based on these multi-omics observations and prior literature, it was hypothesized that immune-lipid interactions may contribute to mood instability in AFD.</p><p><strong>Conclusion: </strong>The exploratory longitudinal pilot study nominates PIAS4-centered immuno-metabolic signals as candidate molecular features of AFD. The findings support the potential utility of longitudinal multi-omics for mapping dynamic biomarker networks in affective disorders. However, larger, independent, medication-informed, and demographically diverse cohorts are required to validate these candidate signatures and clarify their relevance to diagnosis, treatment response, and disease-course monitoring.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705759","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}

{"title":"Bidirectional Neurobiological Interactions Between Cancer and PTSD: Mechanisms and Emerging Therapeutic Implications.","authors":"Zhengrong Zhang, Tong Su, Meng Hui Li, Yang Ge, Hang Gao, Yongfu Zhu, Hang Song, Guoqi Zhu","doi":"10.2174/011570159X468954260722100955","DOIUrl":"https://doi.org/10.2174/011570159X468954260722100955","url":null,"abstract":"<p><strong>Purpose: </strong>This review aims to illustrate the bidirectional neurobiological mechanisms underlying cancer and Post-Traumatic Stress Disorder (PTSD) comorbidity, highlight the active regulatory role of the nervous system, and propose targeted intervention strategies.</p><p><strong>Methods: </strong>This narrative review was conducted by searching PubMed, Google Scholar, and Web of Science for all years up to 2025. The following search terms were combined: \"PTSD\" AND \"Tumor microenvironment\" OR \"Neural circuit\" AND \"cancer\". Of the 1182 articles initially identified, 115 were enrolled in integrative analysis after duplicate removal, initial title/abstract screening, and overall text eligibility.</p><p><strong>Results: </strong>As a traumatic stressor, cancer induces PTSD via diagnostic distress, treatment-related brain structural alterations, fear circuit activation, and neuroinflammation. PTSD, in turn, increases the risk of neoplastic development by disrupting the Hypothalamic-Pituitary-Adrenal (HPA) axis, leading to hyperactivity of the Sympathetic Nervous System (SNS) and restructuring immune functions to create a pro-tumor microenvironment. Moreover, cancer cells can actively hijack neuronal functions to promote malignant progression by forming neuron-tumor synapses, internalizing neuronal mitochondria, and integrating into neural networks. The mechanisms we mentioned in the article - such as tumor synapse formation and transfer of neuronal mitochondria - mainly come from preclinical studies and have not yet obtained direct clinical evidence in humans.</p><p><strong>Discussion: </strong>Mental illness and cancer have a wide positive bidirectional relationship, which poses a challenge to the traditional dichotomy between physical illness and psychological disorders. This highlights the need to integrate mind-body treatment in the practice of oncology and psychiatry.</p><p><strong>Conclusion: </strong>The nervous system is an active regulator and not a passive responder in patients with comorbid cancer and PTSD. Disruption of this pathological cycle requires the development of specific interventions that target neural signaling, metabolic crosstalk, and neuroendocrine pathways.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705692","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}

{"title":"Trace Amine-associated Receptor 1 Agonists for Treatment of Substance use Disorder: Evidence from Rodent Behavioral Studies.","authors":"Barathi Bahavan, Jana Ruda-Kucerova","doi":"10.2174/011570159X493058260722090302","DOIUrl":"https://doi.org/10.2174/011570159X493058260722090302","url":null,"abstract":"<p><p>This narrative review provides evidence regarding the impact of trace amine-associated receptor 1 (TAAR1) agonists on rodent models of substance use disorders (SUDs). We delineated the fundamental aspects of the pharmacodynamics and pharmacokinetics of TAAR1 agonists and collected in vivo studies that investigated TAAR1 activation in behavioral sensitization, conditioned behaviors, or self-administration models. TAAR1 agonists have demonstrated efficacy in suppressing addiction-relevant behaviors associated with cocaine. Their effectiveness is largely consistent across intrinsic activity levels, routes of administration, and experimental protocols. TAAR1 agonists also show certain preliminary promise as amphetamine psychostimulants, nicotine, alcohol, and opioids, but the number of studies remains very small. The reported effects occurred at doses that did not impair natural reward behavior. Moreover, the findings for alcohol use disorder demonstrated efficacy in both male and female subjects. Conversely, opioid studies have presented mixed results, highlighting the need for further investigation. There is a lack of studies examining the effects of TAAR1 agonists in female subjects, which is crucial for understanding potential sex differences in treatment responses. The limited number of research groups working on this topic raises concerns regarding bias and reproducibility. Future research should address these gaps, expand investigations to diverse populations, and replicate findings across laboratories to strengthen evidence for TAAR1 agonists as potential therapeutic agents for cocaine-use disorder.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705708","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}