Current Neuropharmacology最新文献

{"title":"Maternal Multiple Sclerosis and Offspring's Developmental and Behavioral Profile: A Case-control Study.","authors":"Martina Siracusano, Doriana Landi, Elisa Carloni, Chiara Scoppola, Marialaura Ferrara, Assia Riccioni, Lucrezia Arturi, Leonardo Emberti Gialloreti, Mariagrazia Cicala, Francesca Napoli, Cinzia Niolu, Luigi Mazzone, Girolama Alessandra Marfia","doi":"10.2174/011570159X370866250416103923","DOIUrl":"https://doi.org/10.2174/011570159X370866250416103923","url":null,"abstract":"<p><strong>Introduction: </strong>Maternal chronic immune and inflammatory conditions may predispose newborns to atypical developmental trajectories, identifying pregnancy as a key period for the etiopathogenesis of neurodevelopmental disorders. The possible long-term impact of maternal multiple sclerosis (MS) on the offspring's cognitive and behavioral development and its pharmacological treatment during pregnancy is mostly unknown. This study aims to delineate the cognitive and behavioral profile of offsprings exposed to maternal MS, untreated or treated with Natalizumab throughout pregnancy, in comparison to a control group.</p><p><strong>Methods: </strong>We retrospectively enrolled 39 children (23 males; 16 females; mean age 45.82 ± 35.46 months) exposed to maternal MS, untreated or treated with Natalizumab throughout pregnancy, and 36 children (24 males; 12 females, mean age 38.03 ± 21.52 months) of healthy mothers. All offspring underwent a standardized evaluation of their intellectual or developmental quotient, adaptive functioning, and behavioral issues, including symptoms of autism.</p><p><strong>Results: </strong>The clinical profile of the included offspring was characterized by an adequate cognitive profile and a good level of adaptive skills (MS offspring: Griffiths III mean total DQ (N = 30) 114.57; WISC-IV mean Full IQs (N= 9) 115.44; mean ABAS GAC 97.28/Control offspring: Griffiths III mean total DQ (N = 31) 105.42; WISC-IV mean Full IQs (N= 4) 119.25 ± 11.32; mean ABAS GAC 97.82 ± 21.4). Furthermore, no significant behavioural problems or autism symptoms emerged in the entire group, regardless of MS treatment.</p><p><strong>Conclusion: </strong>Offspring's developmental and behavioral phenotypes do not appear to be influenced by maternal treatment with Natalizumab until late pregnancy, nor by maternal variables directly related to MS (age at the time of MS diagnosis, disease duration, and severity).</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575014","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":"Stem Cell Therapy and Models for Autism Spectrum Disorder: Insights and Research.","authors":"Yulong Liu, Yi Luo, Jiayin Liu, Meifeng Gong, Meiling Xia, Xiaotang Fan","doi":"10.2174/011570159X368403250618054913","DOIUrl":"https://doi.org/10.2174/011570159X368403250618054913","url":null,"abstract":"<p><p>Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by impaired social communication, repetitive behavior patterns, and atypical sensory perception. The Autism and Developmental Disabilities Monitoring Network reports that approximately 1 in 36 children are diagnosed with ASD, highlighting the increasing prevalence and the pressing need for innovative treatment approaches. Medications commonly used in ASD primarily aim to manage associated symptoms, as there are currently no FDA-approved medications specifically for treating ASD core symptoms. Stem cells have demonstrated significant potential in cell-based therapies for ASD and have been utilized in in vitro models to investigate the pathogenesis of the condition. This review focuses on the recent advancements in stem cell-based transplantation in animal models of ASD, aiming to explore the improvement of ASD symptoms and the underlying mechanisms involved. It also discussed the application of stem cell-based transplantation in pediatric and adolescent populations with ASD to evaluate treatment efficacy and potential preventive strategies. Furthermore, recent efforts are addressed in developing stem cell-based models for both syndromic and non-syndromic forms of ASD, emphasizing studies that utilize cerebral organoids for modeling ASD, which facilitate the exploration of disease mechanisms within a tissue-like environment.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575015","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":"The Fragile Balance: Autophagy's Role in Neurodegenerative Disease Progression.","authors":"Bharat Bhushan, Meenakshi Dhanawat, Garima, Kashish Wilson, Sumeet Gupta, Samrat Chauhan","doi":"10.2174/011570159X377552250627113915","DOIUrl":"https://doi.org/10.2174/011570159X377552250627113915","url":null,"abstract":"<p><p>Autophagy relates to the mechanism underlying the intracellular constituents' breakdown by lysosomes. Autophagy plays an essential role in preserving and regulating cellular homeostasis by mediating the degradation of intracellular components and recycling their decomposition products. It was demonstrated that autophagy operates in-vivo in the starving reaction, initial growth, internal control of quality, and cell division. Autophagy malfunction is perhaps connected with cancer and neurological conditions, as demonstrated by current research. In conjunction with the identification of specific mutations associated with autophagy-related disorders and deeper knowledge of the pathophysiology of disorders caused by aberrant disintegration of particular autophagy substrates, autophagy activation serves a vital part in prolonging lifespans and suppressing the process of aging. To safeguard the homeostasis within a cell, cells have developed sophisticated quality-control procedures for organelles and proteins. These quality-control mechanisms maintain cellular integrity through degradation by the autophagy-lysosome or ubiquitin-proteasome systems, as well as through protein folding assistance (or refolding of misfolded proteins) provided by molecular chaperones. A great deal of neurodegenerative illnesses are indicated by the development of intracellular inclusions formed from misfolded proteins, which are believed to be an outcome of defective autophagy. Additionally, it was recently discovered that neurodegenerative illnesses are also linked with mutations in key autophagy-related genes. However, pathogenic proteins like α-synuclein and amyloid β cause damage to the autophagy system. This paper examines the recent advancements in our understanding of the link between autophagic abnormalities and the development of neurological disorders, and proposes that activating autophagy could serve as a potential therapeutic strategy.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575016","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":"Exploring Mechanistic Insights by Carotenoids in Neuropathic and Inflammatory Pain.","authors":"Fatemeh Abbaszadeh, Masoumeh Jorjani, Roshanak Amirian, Sajad Fakhri, Haroon Khan","doi":"10.2174/011570159X371386250619064416","DOIUrl":"https://doi.org/10.2174/011570159X371386250619064416","url":null,"abstract":"<p><p>Chronic pain, characterized by persistent discomfort and reduced quality of life, poses a significant challenge for individuals. Chronic pain is predominantly divided into central neuropathic pain, peripheral neuropathic pain, and inflammatory pain. Considering the multiple dysregulated pathways behind such pain conditions, researchers are exploring new multi-target agents that offer enhanced efficacy and reduced side effects of the present drugs. Carotenoids are natural pigments with antioxidant and anti-inflammatory properties found in various fruits, vegetables, and seafood. Through their mechanisms of action, carotenoids have shown promising efficacy in alleviating pain hypersensitivity, reducing inflammation and oxidative stress, and modulating pain-related signaling pathways. This comprehensive review delves into the potential of carotenoids and their derivatives as natural nutraceuticals for managing inflammation and relieving pain. In the current study, the mechanisms of action by which carotenoids exert their beneficial effects during preclinical and clinical studies are provided. This review could pave the road for the application of carotenoids for more pain-related clinical trials and further applications.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559480","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":"Powering Up the Brain: Intercellular Mitochondrial Quality Control and Its Implication in Stroke.","authors":"Xinyu Zhou, Shenzhe Wu, Tianxi Huang, Yue Li, Jianhong Yang, Zhen Gu, Xiangnan Zhang","doi":"10.2174/011570159X388351250620065716","DOIUrl":"https://doi.org/10.2174/011570159X388351250620065716","url":null,"abstract":"<p><p>Mitochondria are critical for neuronal survival and function, and their dysregulation is closely related to the incidence and prevalence of various neurological disorders, including stroke. Mitochondrial quality control (MQC) is vital for maintaining mitochondrial integrity, particularly in neurons. Under ischemic conditions, neurons evolve a range of adaptive strategies to preserve mitochondria function dynamically, either by generating functional mitochondria or by eliminating dysfunctional ones via autophagy, both of which play key roles in keeping neuronal survival under the conditions of stroke. Besides these intracellular strategies, the intercellular mechanisms underlying MQC have been observed in the nervous system. Functional mitochondria from healthy cells can be supplemented to ischemic neurons in distinct manners and thus restore the mitochondrial network of recipient cells. Conversely, injured neurons release dysfunctional mitochondria, which can be further degraded by adjacent glial cells. Alternatively, the discarded mitochondria act as a threat to surrounding cells and can disrupt the homeostasis of the nervous system. In this review, the key discoveries in intercellular MQC in the nervous system were summarized, and further discussed the implications of intercellular MQC strategies for stroke therapy.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539319","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":"Therapeutic Potential of Anesthesiology for Sleep Disorders in the Perioperative Period.","authors":"Xiao-Li Pan, Yu-Fan Xi, Peng Liang, Jiapeng Huang","doi":"10.2174/011570159X368375250611103614","DOIUrl":"https://doi.org/10.2174/011570159X368375250611103614","url":null,"abstract":"<p><p>Sleep is important to maintain normal physiological functions of the human body. With increased stress in modern society, the number of patients suffering from sleep disorders is gradually increasing. Many studies have shown that general anesthetics induce loss of consciousness by acting on the sleep-wake circuit. In recent years, general anesthesia and other anesthetic agents have been used in the diagnosis and treatment of sleep disorders. This article discusses the mechanism of sleep and sleep disorders, summarizes the effects of anesthetics on sleep and their regulatory mechanisms, and reviews the research progress of using anesthetics in the diagnosis and treatment of sleep disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539387","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":"Neuropharmacological Insights into Glutamate Homeostasis in Post-stroke Depression Regulated by Astrocytes.","authors":"Na Zhang, Kaijun Han, Lixinbei Sheng, Fang Wang, Manlan He, Mengqian Wu, Zhen Han, Yichen Li, Lu Chen","doi":"10.2174/011570159X379476250611052236","DOIUrl":"https://doi.org/10.2174/011570159X379476250611052236","url":null,"abstract":"<p><p>Stroke patients often experience multiple functional impairments, including difficulties with swallowing, speech, cognition, and motor skills, which can lead to symptoms such as emotional distress and cognitive deficits. Approximately one-third of post-stroke patients may develop poststroke depression (PSD), significantly hindering recovery and increasing the burden on families and healthcare systems. This review focuses on the underlying mechanisms of PSD, emphasizing the glutamatergic hypothesis. As the primary excitatory neurotransmitter, glutamate plays a central role in neural-signaling. However, excessive glutamate accumulation can cause neuronal damage, making it a key mechanism in the development of PSD. Astrocytes are crucial for maintaining glutamate homeostasis by clearing excess glutamate and regulating its synthesis and transport, thereby preventing excitotoxicity. Following a stroke, astrocytic dysfunction-characterized by overactivation and inflammatory responses-can exacerbate neuronal injury and further contribute to the emergence of depressive symptoms. This article also highlights potential therapeutic approaches targeting the glutamatergic system, such as NMDA receptor antagonists, AMPA receptor antagonists, and modulators of glutamate transporters, as well as other types (e.g., Chinese medicine, herbal medicine, and targeted pathways acting on neurons). These strategies offer promising avenues for PSD treatment. Future studies should delve deeper into the molecular mechanisms by which astrocytes regulate glutamate homeostasis, providing a robust foundation for the precision treatment of post-stroke depression.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539318","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":"Drug-resistant Epilepsy: Which Drugs are Substrates of P-glycoprotein and Which are Not?","authors":"Javier Aylón Val, Virgilio Hernando-Requejo","doi":"10.2174/011570159X381818250612061802","DOIUrl":"https://doi.org/10.2174/011570159X381818250612061802","url":null,"abstract":"<p><p>One of the accepted factors of antiseizure medication resistance is the action of P-glycoprotein (P-gp), limiting the access of drugs to the nervous system. But if we ask which antiseizure medications are substrates of P-gp and which are not, the available bibliography will not allow us to obtain a clear answer. In this review, we focus on clarifying this response. The reviewed studies have been conducted both in cell lines and in mice that have been administered a P-gp inhibitor, artificially induced with drug-resistant epilepsy, or had a P-gp gene knockout. A limited number of studies have been conducted in dogs, primates, brain sections of known epilepsies, or human volunteers, including pharmacokinetic studies in healthy volunteers and symptomatic response to treatment. Notably, in human cases, allele variation studies check if having one allele or another of P-gp varies the pharmacokinetics in question. As we see, the approach to P-gp and antiseizure medication can be done using very different methods, which undoubtedly complicates the interpretation of the findings. We cannot be categorical in our results, but we can mention probabilities. Regarding the weighting of studies, we will consider those conducted in humans as more important, followed by animal studies, and we will give less weight to studies showing contradictory results compared to the Based on the published bibliography, we propose that, general bibliographic base. among the anticrisis medications, the following are likely substrates of P-glycoprotein: Phenytoin, Phenobarbital, Oxcarbazepine, Lamotrigine, Topiramate, and Lacosamide (less evidence). The following are probably not substrates: Brivaracetam, Zonisamide, Valproic acid, Perampanel, Gabapentin, and Vigabatrin. We have not obtained enough information about: Carbamazepine, Eslicarbazepine, Levetiracetam, Tiagabine, Felbamate, Pregabalin, Rufinamide, Ezogabine, and Retigabine.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539317","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":"The role of trace amine-associated receptor 1 (TAAR1) in the pathophysiology and treatment of depression.","authors":"Wei Guan","doi":"10.2174/011570159X370669250526115723","DOIUrl":"https://doi.org/10.2174/011570159X370669250526115723","url":null,"abstract":"<p><p>Depression is a chronic and recurrent psychiatric condition thought to result from an interaction between genetic susceptibility and environmental stimuli. Even though existing available therapies prescribed for depressed patients are effective, it will take several weeks to demonstrate their full effectiveness, and is often accompanied by side effects and withdrawal symptoms. In this regard, discovery of new antidepressant drug of unique, higher curative effect, and less adverse reaction is the pursuit of pharmaceutical. Trace-amine associated receptor 1 (TAAR1), an intracellular G-protein coupled receptor (GPCR) that is broadly expressed in the mammalian brain, especially within cortical, limbic, and midbrain monoaminergic regions and activated by \"trace amines\" (TAs). It is allegedly involved in modulating dopaminergic, serotonergic and glutamatergic transmission, makes TAAR1 a new drug target for the treatment of dysfunction of monoamine-related disorders. What's more, agonist compounds of TAAR1 have generated interest as potential treatments for depression due to TAAR1-mediated regulation of monoamine neurotransmitters. In fact, Ulotaront (a TAAR1 agonist) is reported to be currently undergoing phase 2/3 clinical trials in order to test its safety and efficacy in the treatment of major depressive disorder (MDD). However, details of the mechanism of TAAR1 remain elusive. Thus, this paper aims to review evidence of the potential role of TAAR1 in the pathophysiology and treatment of depression. Moreover, we briefly summarize the recent findings in the elucidation of behavioral and physiological properties of TAAR1 agonists both in clinical trials and preclinical animal studies. Collectively, these studies will provide a solid foundation for TAAR1 as a novel therapeutic target for depression.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539386","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 Proteins in Hypoxia-stressed Astrocyte-Derived Extracellular Vesicles.","authors":"Berenice N Bernal Vicente, Isaac Ponce, Manuel Santos Gutiérrez, Emmanuel Ríos Castro, Luis B Tovar-Y-Romo","doi":"10.2174/011570159X359837250611052037","DOIUrl":"https://doi.org/10.2174/011570159X359837250611052037","url":null,"abstract":"<p><strong>Background: </strong>Mass spectrometry-based proteomic analysis advancements have generated extensive protein data from cells involved in neurodegenerative diseases. The field of neuroproteomics is expanding to include the study of extracellular vesicles (EVs) to identify potential biomarkers for disease prevention and endogenous factors involved in neuroprotection.</p><p><strong>Methods: </strong>In this study, the cortical astrocytes in normoxia were cultured and subjected to hypoxic conditions and obtained astrocyte-derived EVs released in supernatant separately then performed label- free mass spectrometry-based proteomics of these EVs to determine which is the effect of the hypoxic event on the cargo proteins. A meta-analysis of the results compared with previously published databases was conducted. Data was deposited in the ProteomeXchange Consortium with the identified PXD050160.</p><p><strong>Results: </strong>This study revealed a differential expression of 83 upregulated proteins under hypoxic conditions and 61 downregulated proteins under normoxic conditions, highlighting the protective protein signatures elicited by astrocytes.</p><p><strong>Conclusion: </strong>The present study makes a novel contribution by employing proteomic techniques to characterize the protein cargo of EVs isolated from primary rat astrocytes. This approach allows for a more refined analysis of astrocyte-specific intercellular signaling under hypoxic conditions. It offers valuable insights into the roles of astrocytes in maintaining brain homeostasis and contributing to pathological processes.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474194","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}