CNS & neurological disorders drug targets最新文献

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Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease. 探索治疗策略:阿尔茨海默病中代谢紊乱与 FOXO 信号之间的关系。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273321002240919102841
Parneet Kaur, Heena Khan, Amarjot Kaur Grewal, Kamal Dua, Sachin Kumar Singh, Gaurav Gupta, Thakur Gurjeet Singh
{"title":"Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease.","authors":"Parneet Kaur, Heena Khan, Amarjot Kaur Grewal, Kamal Dua, Sachin Kumar Singh, Gaurav Gupta, Thakur Gurjeet Singh","doi":"10.2174/0118715273321002240919102841","DOIUrl":"10.2174/0118715273321002240919102841","url":null,"abstract":"<p><p>Alzheimer's disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world's population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"196-207"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unravelling the Role of Tyrosine and Tyrosine Hydroxylase in Parkinson's Disease: Exploring Nanoparticle-based Gene Therapies. 揭示酪氨酸和酪氨酸羟化酶在帕金森病中的作用:探索基于纳米颗粒的基因治疗。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273336139241211071748
Satya Eswari Jujjavarapu, Arnav Mishra
{"title":"Unravelling the Role of Tyrosine and Tyrosine Hydroxylase in Parkinson's Disease: Exploring Nanoparticle-based Gene Therapies.","authors":"Satya Eswari Jujjavarapu, Arnav Mishra","doi":"10.2174/0118715273336139241211071748","DOIUrl":"10.2174/0118715273336139241211071748","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder that results from the progressive loss of neurons in the brain followed by symptoms such as slowness and rigidity in movement, sleep disorders, dementia and many more. The different mechanisms due to which the neuronal degeneration occurs have been discussed, such as mutation in PD related genes, formation of Lewy bodies, oxidation of dopamine. This review discusses current surgical treatment and gene therapies with novel developments proposed for PD. Gene therapy based on novel approaches will possess more potential advantages over the conventional methods. Currently, gene therapy for such disorders is still under the process of clinical trials and approval. The pathogenesis comes from the breakdown of dopaminergic neurons within substantia nigra (SN) by the action of tyrosinase enzyme and subsequent accumulation of α-synuclein within the neurons. These dopaminergic neurons are the main source of dopamine, the decline of which is responsible for the symptoms. So, gene therapy can possibly provide more stable supplementation and regulate the expression of tyrosinase enzyme, providing better symptomatic relief and lesser side effects. Dopamine replacement therapy is a wellstudied gene therapy method for PD. Another approach involves introducing functional genes for enzymes such as tyrosine hydroxylase, cyclohydrolases, and decarboxylases with the help of engineered vectors such as AAV and LV. Further, the potential application of nanoparticles in gene therapy as an efficient gene delivery and imaging system has been discussed. Among these, lipidbased nanoparticles such as PILs offer important benefits in terms of enhanced bioavailability, permeability to the cells, and solubility. So, this review paper summarizes some of the advanced gene therapy approaches for PD and the current status of clinical research in the development of gene therapy using nanoparticles.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"325-339"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revolutionising Neurological Therapeutics: Investigating Drug Repurposing Strategies. 神经病学疗法的革命:研究药物再利用战略。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273329531240911075309
Meenakshi Attri, Asha Raghav, Jyoti Sinha
{"title":"Revolutionising Neurological Therapeutics: Investigating Drug Repurposing Strategies.","authors":"Meenakshi Attri, Asha Raghav, Jyoti Sinha","doi":"10.2174/0118715273329531240911075309","DOIUrl":"10.2174/0118715273329531240911075309","url":null,"abstract":"<p><p>Repurposing drugs (DR) has become a viable approach to hasten the search for cures for neurodegenerative diseases (NDs). This review examines different off-target and on-target drug discovery techniques and how they might be used to find possible treatments for non-diagnostic depressions. Off-target strategies look at the known or unknown side effects of currently approved drugs for repositioning, whereas on-target strategies connect disease pathways to targets that can be treated with drugs. The review highlights the potential of experimental and computational methodologies, such as machine learning, proteomic techniques, network and genomics-based approaches, and in silico screening, in uncovering new drug-disease correlations. It also looks at difficulties and failed attempts at drug repurposing for NDs, highlighting the necessity of exact and standardised procedures to increase success rates. This review's objectives are to address the purpose of drug repurposing in human disorders, particularly neurological diseases, and to provide an overview of repurposing candidates that are presently undergoing clinical trials for neurological conditions, along with any possible causes and early findings. We then include a list of drug repurposing strategies, restrictions, and difficulties for upcoming research.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"115-131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent Development of Zolmitriptan Formulation in Migraine Therapy: Production, Metabolism and Pharmaceutical Aspects. 用于偏头痛治疗的佐米曲普坦制剂的最新发展:生产、代谢和制药方面。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273306929240820071521
Farha Bano, Faris F Aba Alkhayl, Mohammad Rashid, Mohammed Ghanim Alqethami, Mohammed Omair Alsufyani, Khadijah Oudah R Alhothali, Mohammed Japer Mohammed Hakme, Abdulrahman Mohammed Al-Jarallah, Rikeshwer Prasad Dewangan, Asif Husain
{"title":"Recent Development of Zolmitriptan Formulation in Migraine Therapy: Production, Metabolism and Pharmaceutical Aspects.","authors":"Farha Bano, Faris F Aba Alkhayl, Mohammad Rashid, Mohammed Ghanim Alqethami, Mohammed Omair Alsufyani, Khadijah Oudah R Alhothali, Mohammed Japer Mohammed Hakme, Abdulrahman Mohammed Al-Jarallah, Rikeshwer Prasad Dewangan, Asif Husain","doi":"10.2174/0118715273306929240820071521","DOIUrl":"10.2174/0118715273306929240820071521","url":null,"abstract":"<p><p>The triptans class of pharmaceuticals, which was created to treat acute migraine, is made up of indole-containing drugs that bind to a subset (1B/1D) of 5-hydroxytryptamine receptors and are agonists of serotonin receptors. At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists. Zolmitriptan, a synthetic tryptamine derivative and a well-known member of the triptan family, is available as an orally disintegrating tablet, nasal spray, and tablet. There are melt formulations of rizatriptan and zolmitriptan available on the market that are easier to use and absorb, comparable to regular pills. Recently, the FDA approved zolmitriptan, a medication with tolerability comparable to sumatriptan. Whereas zolmitriptan is only available as an oral melt or tablet, sumatriptan is available as a nasal spray, oral preparation, or self-injectable kit. The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine. However, zolmitriptan binds to plasma proteins only 25% of the time because of significant first-pass degradation. Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"219-233"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An Overview of the Natural Neuroprotective Agents for the Management of Cognitive Impairment Induced by Scopolamine in Zebrafish (Danio rerio). 管理东莨菪碱诱导的斑马鱼(Danio rerio)认知障碍的天然神经保护剂概述。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273309256240702053609
Sara Abidar, Lucian Hritcu, Mohamed Nhiri
{"title":"An Overview of the Natural Neuroprotective Agents for the Management of Cognitive Impairment Induced by Scopolamine in Zebrafish (<i>Danio rerio</i>).","authors":"Sara Abidar, Lucian Hritcu, Mohamed Nhiri","doi":"10.2174/0118715273309256240702053609","DOIUrl":"10.2174/0118715273309256240702053609","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a neurodegenerative disorder mainly characterized by dementia and cognitive decline. AD is essentially associated with the presence of aggregates of the amyloid-β peptide and the hyperphosphorylated microtubule-associated protein tau. The available AD therapies can only alleviate the symptoms; therefore, the development of natural treatments that exhibit neuroprotective effects and correct the behavioral impairment is a critical requirement. The present review aims to collect the natural substances that have been evaluated for their neuroprotective profile against AD-like behaviors induced in zebrafish (<i>Danio rerio</i>) by scopolamine. We focused on articles retrieved from the PubMed database via preset searching strings from 2010 to 2023. Our review assembled 21 studies that elucidated the activities of 28 various natural substances, including bioactive compounds, extracts, fractions, commercial compounds, and essential oils. The listed compounds enhanced cognition and showed several mechanisms of action, namely antioxidant potential, acetylcholinesterase's inhibition, and reduction of lipid peroxidation. Additional studies should be achieved to demonstrate their preventive and therapeutic activities in cellular and rodent models. Further clinical trials would be extremely solicited to support more insight into the neuroprotective effects of the most promising drugs in an AD context.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"21-31"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors. 帕金森病:揭示杂环单胺氧化酶-B 抑制剂的药用前景和最新发展。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273340983241018095529
Neha Rana, Parul Grover
{"title":"Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors.","authors":"Neha Rana, Parul Grover","doi":"10.2174/0118715273340983241018095529","DOIUrl":"10.2174/0118715273340983241018095529","url":null,"abstract":"<p><p>Parkinson's disease is a neurodegenerative condition characterized by slow movement (bradykinesia), tremors, and muscle stiffness. These symptoms occur due to the degeneration of dopamine- producing neurons in the substantia nigra region of the brain, leading to reduced dopamine levels. The development of Parkinson's Disease (PD) involves a combination of genetic and environmental factors. PD is associated with abnormal regulation of the monoamine oxidase (MAO) enzyme. Monoamine oxidase inhibitors (MAOIs) are an important class of drugs used to treat PD and other neurological disorders. In the early stages of PD, monotherapy with MAO-B inhibitors has been shown to be both safe and effective. These inhibitors are also commonly used as adjuncts in long-term disease management, as they can improve both motor and non-motor symptoms, reduce \"OFF\" periods, and potentially slow disease progression. However, current MAO-B inhibitors come with side effects like dizziness, nausea, vomiting, light-headedness, and fainting. Therefore, accelerating the development of new MAO-B inhibitors with fewer side effects is crucial. This review explores natural compounds that may inhibit monoamine oxidase B (MAO-B), focusing on key findings from the past seven years. It highlights the most effective heterocyclic compounds against MAO-B, including thiazolyl hydrazone, pyridoxine-resveratrol, pyridazine, isoxazole, oxadiazole, benzothiazole, benzoxazole, coumarin, caffeine, pyrazoline, piperazine, piperidine, pyrrolidine, and morpholine derivatives. The review covers <i>in vitro, in silico</i>, and <i>in vivo</i> data, along with the structure- activity relationship of these compounds. These findings offer valuable insights for the development of more effective MAO-B inhibitors and advancements in Parkinson's disease research.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"263-284"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuroprotective Efficacy and Complementary Treatment with Medicinal Herbs: A Comprehensive Review of Recent Therapeutic Approaches in Epilepsy Management. 神经保护功效与药草辅助治疗:最新癫痫治疗方法综述》。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273332140240724093837
Amit Anand, Aman Shrivastava, Kuldeep Singh, Rakesh Barik, Devshree Gayakwad, S Jailani, Shamim, Sumeet Dwivedi
{"title":"Neuroprotective Efficacy and Complementary Treatment with Medicinal Herbs: A Comprehensive Review of Recent Therapeutic Approaches in Epilepsy Management.","authors":"Amit Anand, Aman Shrivastava, Kuldeep Singh, Rakesh Barik, Devshree Gayakwad, S Jailani, Shamim, Sumeet Dwivedi","doi":"10.2174/0118715273332140240724093837","DOIUrl":"10.2174/0118715273332140240724093837","url":null,"abstract":"<p><p>Central Nervous System (CNS) disorders affect millions of people worldwide, with a significant proportion experiencing drug-resistant forms where conventional medications fail to provide adequate seizure control. This abstract delves into recent advancements and innovative therapies aimed at addressing the complex challenge of CNS-related drug-resistant epilepsy (DRE) management. The idea of precision medicine has opened up new avenues for epilepsy treatment. Herbs such as curcumin, ginkgo biloba, panax ginseng, bacopa monnieri, ashwagandha, and rhodiola rosea influence the BDNF pathway through various mechanisms. These include the activation of CREB, inhibition of NF-κB, modulation of neurotransmitters, reduction of oxidative stress, and anti- inflammatory effects. By promoting BDNF expression and activity, these herbs support neuroplasticity, cognitive function, and overall neuronal health. Novel antiepileptic drugs (AEDs) with distinct mechanisms of action demonstrate efficacy in refractory cases where traditional medications falter. Additionally, repurposing existing drugs for antiepileptic purposes presents a cost-effective strategy to broaden therapeutic choices. Cannabidiol (CBD), derived from cannabis herbs, has garnered attention for its anticonvulsant properties, offering a potential adjunctive therapy for refractory seizures. In conclusion, recent advances and innovative therapies represent a multifaceted approach to managing drug-resistant epilepsy. Leveraging precision medicine, neurostimulation technologies, novel pharmaceuticals, and complementary therapies, clinicians can optimize treatment outcomes and improve the life expectancy of patients living with refractory seizures. Genetic testing and biomarker identification now allow for personalized therapeutic approaches tailored to individual patient profiles. Utilizing next-generation sequencing techniques, researchers have elucidated genetic mutations.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"60-73"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways. 联合使用罗格列酮和益生菌载体固体脂质纳米颗粒增强实验性多发性硬化症的神经保护:细胞信号通路的调节。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273336107241015100912
Nitish Kumar, Nidhi Tyagi, Sidharth Mehan, Alok Pratap Singh
{"title":"Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways.","authors":"Nitish Kumar, Nidhi Tyagi, Sidharth Mehan, Alok Pratap Singh","doi":"10.2174/0118715273336107241015100912","DOIUrl":"10.2174/0118715273336107241015100912","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a persistent autoimmune condition characterized by inflammation and neurodegeneration. The current efficacy of treatments is limited, which has generated interest in developing neuroprotective strategies. Solid lipid nanoparticles (SLNs) and probiotics are potential drug delivery vehicles for targeting the CNS (Central nervous system), regulating immune responses, and supporting neuroprotection in neurological conditions.</p><p><strong>Methods: </strong>The study investigates how SLNs containing RSG (rosiglitazone) and probiotics can protect the nervous system in cases of MS. We administered toxin EtBr (Ethidium bromide) from day 1 to day 7, later followed by the treatment from day 8 to day 35. During this time interval, various behavioural parameters have been performed. Further, after 35th day, blood plasma of animals was collected to study complete CBC profiling and animals were sacrificed. Then, biochemical and molecular studies, gross morphology of brain sectioning, histopathological evaluation and estimation of fatty acid content in fecal matter were performed.</p><p><strong>Results: </strong>RSG shows neuroprotective effects by blocking the STAT-3 and mTOR signaling pathways and increasing the production of PPAR-gamma. GW9662, a PPAR-gamma antagonist given at a dose of 2 mg/kg (i.p), was utilized to evaluate the role of PPAR-gamma and to compare the efficacy of RSG and probiotic-loaded SLNs in potentially providing neuroprotection. The relationship between RSG and the STAT-3, mTOR, and PPAR-gamma pathways in MS was confirmed and validated using <i>in-silico</i> analysis. RSG and probiotic-loaded SLNs modulate the complete blood profiling of rats and improve the symptoms of MS. We assessed the diagnostic capabilities of different biological samples such as cerebrospinal fluid, blood plasma, and brain homogenates (specifically from the hippocampus, striatum, cortex, and midbrain) to analyze neurochemical changes linked to neurobehavioral changes in the progression of MS.</p><p><strong>Conclusion: </strong>The study showed that combining RSG and probiotics in an experimental medication form improved symptoms of MS more effectively than using RSG alone. This improvement is likely due to changes in STAT-3, mTOR, and PPAR-gamma signaling pathways.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"285-324"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide. 创伤性脑损伤后的神经表现:行为、神经炎症、兴奋毒性、Nrf-2 和一氧化氮的作用。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273318552240708055413
Lav Goyal, Shamsher Singh
{"title":"Neurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide.","authors":"Lav Goyal, Shamsher Singh","doi":"10.2174/0118715273318552240708055413","DOIUrl":"10.2174/0118715273318552240708055413","url":null,"abstract":"<p><p>Traumatic Brain Injury (TBI) is attributed to a forceful impact on the brain caused by sharp, penetrating bodies, like bullets and any sharp object. Some popular instances like falls, traffic accidents, physical assaults, and athletic injuries frequently cause TBI. TBI is the primary cause of both mortality and disability among young children and adults. Several individuals experience psychiatric problems, including cognitive dysfunction, depression, post-traumatic stress disorder, and anxiety, after primary injury. Behavioral changes post TBI include cognitive deficits and emotional instability (anxiety, depression, and post-traumatic stress disorder). These alterations are linked to neuroinflammatory processes. On the other hand, the direct impact mitigates inflammation insult by the release of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF-α, exacerbating neuronal injury and contributing to neurodegeneration. During the excitotoxic phase, activation of glutamate subunits like NMDA enhances the influx of Ca<sup>2+</sup> and leads to mitochondrial metabolic impairment and calpain-mediated cytoskeletal disassembly. TBI pathological insult is also linked to transcriptional response suppression Nrf-2, which plays a critical role against TBI-induced oxidative stress. Activation of NRF-2 enhances the expression of anti-oxidant enzymes, providing neuroprotection. A possible explanation for the elevated levels of NO is that the stimulation of NMDA receptors by glutamate leads to the influx of calcium in the postsynaptic region, activating NOS's constitutive isoforms.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"47-59"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series. 高纯度大麻二酚对难治性和超难治性癫痫状态的疗效:病例系列。
CNS & neurological disorders drug targets Pub Date : 2025-01-01 DOI: 10.2174/0118715273304077240603115521
Giovanni Di Mauro, Giovanni Vietri, Loreta Quaranta, Fabio Placidi, Francesca Izzi, Alessandro Castelli, Andrea Pagano, Francesca Leonardis, Viviana De Angelis, Ciro Bianco, Maria Grazia Celeste, Nicola Biagio Mercuri, Claudio Liguori
{"title":"Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series.","authors":"Giovanni Di Mauro, Giovanni Vietri, Loreta Quaranta, Fabio Placidi, Francesca Izzi, Alessandro Castelli, Andrea Pagano, Francesca Leonardis, Viviana De Angelis, Ciro Bianco, Maria Grazia Celeste, Nicola Biagio Mercuri, Claudio Liguori","doi":"10.2174/0118715273304077240603115521","DOIUrl":"10.2174/0118715273304077240603115521","url":null,"abstract":"<p><strong>Introduction: </strong>Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment for these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome, Dravet syndrome, and Tuberous Sclerosis Complex.</p><p><strong>Case presentation: </strong>Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures.</p><p><strong>Conclusion: </strong>According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"158-163"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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