CNS & neurological disorders drug targets最新文献

{"title":"Challenges in Brain Drug Delivery for Neurodegenerative Disorders and Recent Trends: A Review.","authors":"Ashif Anjukandan, Rajaganapathy Kaliyaperumal","doi":"10.2174/0118715273453002260416115852","DOIUrl":"https://doi.org/10.2174/0118715273453002260416115852","url":null,"abstract":"<p><strong>Introduction: </strong>Age-related disorders known as neurodegenerative illnesses are defined by uncontrolled neuronal loss that gradually impairs brain function. The majority of age-related neurodegenerative disorders are caused by dementias, in particular. Nowadays, the neurodegenerative disorders are not limited to age and are reported in all age groups. The drug delivery to treat the neurodegenerative disorders is challenging due to the presence of the blood-brain barrier (BBB).</p><p><strong>Method: </strong>A critical literature review has been conducted across databases such as Scopus, Embase, Cochrane, and PubMed. Blood-brain barrier, neurodegenerative disorders, novel drug delivery system, and targeted drug therapy were the search terms.</p><p><strong>Results: </strong>Neurodegenerative Diseases (NDD) impact the peripheral nervous system, nerve cells, muscles, and the nerve-muscle junction. This term broadly encompasses cognitive disorders, such as Alzheimer's disease, Lewy body dementia, frontotemporal dementia, and vascular dementia. Additionally, other neurodegenerative conditions such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and spinocerebellar ataxias predominantly impair motor system function and nerves in the limbs. The existing therapeutic approaches to treat neurological diseases exhibit limited efficacy due to the BBB. This highly selective semipermeable membrane permits vital nutrients to enter the brain while blocking the potentially harmful toxins. It makes it very challenging to get medications into the brain. There are several effective approaches to deliver drugs to the brain (nanocarrier systems, intranasal administration, and focused ultrasound) to address the limitations of conventional treatments.</p><p><strong>Conclusion: </strong>This review discusses neurodegenerative disorders, brain anatomy/physiology, barriers to drug delivery, and strategies to overcome these limitations.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944234","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}

{"title":"Brigatinib in ALK-fused, Low-grade Pediatric Angiocentric Glioma with Multiple Extracranial Metastases: A Case Report.","authors":"Tao Liu, Ge Shen, Xiaoyan Zhou, Gairong Zhang, Lei Zou","doi":"10.2174/0118715273437006260423091450","DOIUrl":"https://doi.org/10.2174/0118715273437006260423091450","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are the most frequent Central Nervous System (CNS) tumors in children and adolescents. Angiocentric glioma is a rare subtype of pediatric-type diffuse low-- grade gliomas with a relatively favorable prognosis following gross total resection. More recently, the identification of Anaplastic Lymphoma Kinase (ALK) fusions in glioma has led to the development of targeted therapeutics to improve responses and outcomes.</p><p><strong>Case presentation: </strong>Here, we report a 10-year-old boy with pediatric low-grade glioma harboring a KIF5B-ALK fusion. He achieved a durable partial response to the ALK inhibitor brigatinib. The patient presented with nasal congestion, dizziness, and headache. MRI and CT scans revealed multiple masses in the brain, lung, and bone. Pathological review indicated a low-grade glioma, and genetic testing identified a KIF5B-ALK fusion. After surgical resection and molecular diagnosis, the patient was treated with brigatinib. This resulted in rapid tumor reduction and complete remission at 23 months, with no significant adverse effects.</p><p><strong>Conclusion: </strong>This case highlights the importance of molecular profiling in guiding targeted therapies for rare pediatric gliomas. Further research is needed to address questions regarding the optimal use of ALK inhibitors and their long-term impact on prognosis and neurocognitive development.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944226","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}

{"title":"Neuroinflammatory and Synaptic Roles of Glial Cells in Autism Spectrum Disorder.","authors":"Tavleen Kaur, Dushyant, Neha Yadav, Vishakha Saini, Rupa Devi, Ashwani K Dhingra","doi":"10.2174/0118715273449946260424134921","DOIUrl":"https://doi.org/10.2174/0118715273449946260424134921","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and repetitive behavior. Early indicators are that glial cells-astrocytes, microglia, and oligodendrocytes-are at the center of the etiology and pathogenesis of ASD. A systematic review of literature studies examining glial cell pathology in ASD was conducted. Peer-reviewed literature on astrocyte function, microglial phenotypes, oligodendrocyte-mediated connectivity, and molecular pathways of neurotransmission and neuroinflammation was searched in databases. Astrocytes, playing a crucial role in synaptogenesis and neurotransmitter modulation, exhibit disrupted calcium signaling and increased IL-6 expression in ASD, potentially leading to neuroinflammation and synaptic injury. Microglia, maintaining synaptic homeostasis, become pro-inflammatory (M1) in ASD, which produces cytokines that destroy neurons. Disrupted oligodendrocyte function is linked to aberrant myelination and disrupted neural connectivity. Molecular mechanisms underlie dysregulated activation of toll-like receptors, cytokine signaling, oxidative stress, and dysregulation of glutamate/GABA metabolism. Environmental toxins like chlorpyrifos aggravate excitatory signaling and glial dysfunction. Most of the features of ASD are caused by these glial disorders. Interventions to correct glial dysfunction-e.g., anti-inflammatory medication (e.g., minocycline, ibudilast), gene therapy, and stem cell therapy-are investigated for their potential to restore glia to normal and diminish ASD symptoms. Understanding glial-neuronal communication mechanisms and their role in neuroinflammation offers a hopeful future for accurate, target-specific treatment. Advances in the elucidation of these processes will foretell an enormous increase in therapeutic efficacy and quality of life for individuals with ASD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944042","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}

{"title":"Targeted Nanotechnology Approaches to Bypass the Blood-brain Barrier in Neurodegenerative Disorders.","authors":"Jayasurya Ramesh, B Jayanthi, Vasanth Kumar Mohan, S Srinivasan, M K Vijayalakshmi, Magesh Mohan","doi":"10.2174/0118715273444679260416064255","DOIUrl":"https://doi.org/10.2174/0118715273444679260416064255","url":null,"abstract":"<p><p>Neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are a growing health burden across the world because of the progressive loss of brain cells and the ineffective nature of the available treatment. One significant challenge in the treatment of these conditions is the Blood- -Brain Barrier (BBB), a highly selective interface that limits the access of most therapeutic molecules to the central nervous system. Nanotechnology has become an attractive approach to addressing this difficulty, as it enables the delivery of drugs with high accuracy and actively engages in the repair of the BBB. This review provides an overall synthesis of focused nanotechnology solutions aimed at both circumventing and restoring BBB function in neurodegenerative illnesses. It discusses various nanoparticle (NP) platforms such as polymeric, lipid-based, micellar, metallic, and carbon-derived systems in the light of their physicochemical aspects, transport across the BBB, and therapeutic efficacy. Particular emphasis is put on the receptor-mediated transcytosis, neurovascular unit modulations, and the regulation of Wnt, Shh, and Tie-2 signalling pathways, which are BBB integrity pathways. The review incorporates mechanisms of BBB repair in combination with neuroprotective nanotherapies, rather than focusing solely on end repair. This review covers the role of targeted nanotechnology in the future of therapeutic approaches for neurodegenerative diseases. By connecting materials science, molecular neuroscience, and clinical innovation, it demonstrates how next-generation brain-targeted therapies can be developed using targeted nanotechnology.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944184","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}

{"title":"Synthetic Imidazole Derivatives as Multitarget Agents in Depression: Insights into Mechanism and Therapeutic Promise.","authors":"Shrutika G Kulat, Kalyani Thombre, Krishna Radheshyam Gupta, Milind Janrao Umekar","doi":"10.2174/0118715273434938260408063852","DOIUrl":"https://doi.org/10.2174/0118715273434938260408063852","url":null,"abstract":"<p><p>Depression is a complex neuropsychiatric disorder and one of the chief causes of disability in the world. It is also associated with many patients having poor symptom relief under pharmacological treatments, as well as delayed response and side effects. Recent studies have focused on the fact that synthetic imidazole analogs, with varied biochemical properties, can enhance the efficacy of antidepressants. The literature search was based on databases such as PubMed, Scopus, and ScienceDirect, containing articles uploaded as of 2017 with keywords related to the antidepressant properties and mechanisms of imidazole derivatives. The pertinent preclinical and clinical studies on the antidepressant and neuroprotective effects of synthetic imidazole compounds were included. Imidazole derivatives have interesting antidepressant properties through various indirect actions such as the inhibition of TNF-α and COX-2, modulation of GABA neurotransmitter, and metal ion chelation. Moreover, these compounds effectively cross the blood-brain barrier, modulate dopaminergic and serotonergic systems, and possess strong antioxidant properties, thereby enhancing mitochondrial and neuronal integrity. The multifunctionality of imidazole-based derivatives enables them to interact with central and peripheral processes of depression to regulate neuroinflammation and neurotransmitter balance, unlike traditional antidepressants. However, most evidence remains preclinical, and the barriers include structural variability, limited clinical use, and a lack of stable safety data. It is immediately becoming urgent to conduct large clinical trials and structure-activity relationship studies to support their effectiveness and optimize their pharmacological properties. Synthetic imidazole analogs are upcoming multitasking antidepressants that may be able to address both neuroinflammatory and neurodegenerative facets of depression. Further study of these compounds can help develop next-generation antidepressants that are more effective and have better safety profiles.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944139","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}

{"title":"Tirofiban-Nimodipine Combination Therapy for Early Neurological Deterioration in Small Artery Occlusion Stroke: A Retrospective Cohort Study.","authors":"Changhong Tan, Jiali Yang, Qian Yang, Hui Yang, Jun Liu, Yin Zhang, Junyuan Tian, Lijiang Huang, Baozhen Zeng, Xuefen Wu, Xiaopeng Feng","doi":"10.2174/0118715273443970251226074219","DOIUrl":"https://doi.org/10.2174/0118715273443970251226074219","url":null,"abstract":"<p><strong>Introduction: </strong>Early neurological deterioration (END) affects approximately 30% of patients with small artery occlusion (SAO) stroke. The combination of tirofiban and nimodipine may simultaneously address microthrombosis and vasospasm, two key mechanisms underlying SAOrelated END.</p><p><strong>Methods: </strong>In this retrospective cohort study, we analyzed data from consecutive SAO-END patients treated within two hours of END onset between January 2023 and December 2024. The combination group (n=50) received tirofiban plus nimodipine, while the control group (n=53) received tirofiban alone. The primary outcome was early neurological improvement (ENI), defined as a ≥ 2-point reduction in NIHSS score or ≥ 1-point improvement in motor function at 7 days or discharge. Secondary outcomes included a favorable functional outcome (mRS ≤2) at 90 days and safety events.</p><p><strong>Results: </strong>The combination group demonstrated significantly higher rates of ENI (76% vs. 47.2%; adjusted odds ratio [aOR] 3.96, 95% CI 1.32-11.90; p=0.014) and improved 90-day functional outcomes (84% vs. 58.5%; aOR 4.744, 95% CI 1.212-18.567; p=0.025). Higher admission NIHSS scores (aOR 0.759, 95% CI 0.612-0.941; p=0.012) and diabetes (aOR 0.201, 95% CI 0.048-0.840; p=0.028) were inversely associated with ENI. Older age (aOR 0.933, 95% CI 0.876-0.994; p=0.032) and higher admission NIHSS score (aOR 0.592, 95% CI 0.447-0.784; p=0.000) were negatively correlated with 90-day outcomes. Safety profiles were comparable between groups, with no instances of intracranial hemorrhage or hypotension. The addition of nimodipine did not significantly affect blood pressure.</p><p><strong>Discussion: </strong>Combining tirofiban and nimodipine may improve outcomes in SAO-related early neurological deterioration. If validated in future randomized trials, this combination could address a significant unmet need in a common stroke subtype with high risk of deterioration, potentially influencing clinical practice and guiding further research into multimodal neuroprotection strategies for cerebral small vessel disease.</p><p><strong>Conclusion: </strong>Tirofiban-nimodipine combination therapy was found to be associated with enhanced early neurological recovery in SAO-END patients, warranting further investigation through larger multicenter randomized controlled trials.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944224","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}

{"title":"Future of Preclinical Depression Research: A Perspective of Behavioral Models with Validity and Translational Potential Description.","authors":"Arzoo Pannu, Uma Agarwal","doi":"10.2174/0118715273445992260410072951","DOIUrl":"https://doi.org/10.2174/0118715273445992260410072951","url":null,"abstract":"<p><p>Depression is a complicated mental disorder that has a high rate of occurrence all over the world and still ranks as the main reason for the occurrence of both disability and death. Although a lot has been discovered, the neurobiological mechanisms underlying depression are still not fully comprehended, and the current pharmacotherapies, most of the time, are not enough to bring about the desired results, thus leading to a large number of patients with treatment-resistant symptoms. Animal models, especially those in rodents, are crucial in the entire process of discovering the mechanisms of depression and evaluating new therapeutic strategies. This paper introduces a critical perspective on the different models and behavioral paradigms that are frequently utilized to simulate depressive-like phenotypes such as anhedonia, hopelessness, apathy, cognitive dysfunction, anxiety, and social withdrawal, among others. A major focus is placed on the dimensions of model validity-construct, face, and predictive validity-as well as reliability, which collectively determine the translational potential of animal studies. Importantly, this article focuses on the Species, Strain, and Sex framework as a guiding principle for model selection, emphasizing its value in improving reproducibility and generalizability across studies. Key paradigms such as Chronic Mild Stress (CMS), Learned Helplessness (LH), Chronic Social Defeat Stress (CSDS), and pharmacological models are evaluated in terms of their strengths, limitations, and relevance to human depressive disorders. In addition, behavioral assays, including Forced Swim Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), Sucrose Preference Test (SPT), and social interaction paradigms, are discussed for their utility in assessing depressive-like behaviors and antidepressant efficacy. Finally, the review highlights the need for refinement and innovation in preclinical depression research. A better integration of neurobiological insights with carefully chosen animal models will enhance translational validity, aid the discovery of novel therapeutic targets, and improve clinical outcomes for depressive disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943968","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}

{"title":"Immunoregulatory Effect of Curcumin on Experimental Autoimmune Encephalomyelitis (EAE), an Animal Model of Multiple Sclerosis (MS).","authors":"Mahshid Sadat Ghafelehbashiha, Behrouz Robat-Jazi, Negar Zand Miralvand, Fatemeh Abedini, Azadeh Khalvandi, Ali Akbar Saboor-Yaraghi","doi":"10.2174/0118715273439201260427191018","DOIUrl":"https://doi.org/10.2174/0118715273439201260427191018","url":null,"abstract":"<p><p>Demyelination and progressive neurodegeneration within the central nervous system (CNS) are hallmarks of multiple sclerosis (MS), a chronic autoimmune disease. This review critically assesses the therapeutic efficacy of curcumin-a polyphenolic compound from the rhizome of Curcuma longa turmeric-in experimental autoimmune encephalomyelitis, a well-recognized animal model of MS. The significant anti-inflammatory and antioxidant properties of curcumin help slow the development of EAE. By suppressing pro-inflammatory cytokines, including interleukin-12 (IL-12), interleukin-17 (IL-17), and interferon-gamma (IFN-γ), curcumin mechanistically modifies immune responses while enhancing anti-inflammatory pathways through the upregulation of regulatory T cells (Tregs) and promotion of T helper 2 immune responses. At the same time, it enhances antiinflammatory pathways by upregulating Tregs and promoting T helper 2 (Th2) immune responses. Curcumin also has neuroprotective qualities by increasing the expression of neurotrophic factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which promote remyelination and maintain the viability of neurons. In addition, curcumin changes important intracellular signaling pathways, such as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, which help to preserve the integrity of the blood-brain barrier (BBB) and reduce oxidative stress. Despite challenges associated with curcumin's bioavailability and pharmacokinetics, innovative delivery systems such as polymerized nano-curcumin and exosome-encapsulated formulations show promise in enhancing its therapeutic efficacy. Curcumin appears to be a promising adjunctive therapy for MS, requiring further clinical research to optimize its application in MS care.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943947","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}

{"title":"From Microbes to Minds: The Impact of Gut Bacteria on Infant Cognitive Growth.","authors":"Monireh Rahimkhani, Maryam Hosseini","doi":"10.2174/0118715273391751251125075624","DOIUrl":"https://doi.org/10.2174/0118715273391751251125075624","url":null,"abstract":"<p><p>Recent advances underscore the pivotal role of the gut microbiota in shaping infant brain development, emphasizing how the diversity and function of microbial communities regulate neurodevelopmental processes. This review synthesizes current literature on how maternal and early-life microbial exposures influence the infant gut ecosystem, producing cascading effects on cognitive and behavioral outcomes. Perturbations in gut microbial composition during sensitive developmental windows may increase the risk of conditions such as autism spectrum disorder (ASD) and attention- deficit/hyperactivity disorder (ADHD). Furthermore, research highlights the significance of the gut-brain axis, particularly the impact of nutrition and environmental factors on both microbiome composition and neurodevelopment. This review aims to provide an integrated overview of current evidence and to outline future directions for microbiota-targeted interventions that may enhance cognitive and neurological outcomes in children.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944025","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}

{"title":"Parthenolide: Unlocking the Multitarget Molecular Regulatory Network of Neurological Diseases.","authors":"Yifan Jiang, Xiaoyu Zhang, Yiyang Sun, Tiantian Hou, Longtao Zhang, Yujie Li, Yuxia Ma","doi":"10.2174/0118715273441569260210173840","DOIUrl":"https://doi.org/10.2174/0118715273441569260210173840","url":null,"abstract":"<p><strong>Introduction: </strong>Neurological diseases with a complex etiology and diagnostic complexities are one of the major causes of disability and death globally. In previous preclinical studies, it has been shown that parthenolide (PTL) can provide significant neuroprotective potential. The review synthesizes the mechanistic data on PTL that explains the routes to therapy and creates a strong theoretical framework for future research and drug development.</p><p><strong>Methods: </strong>This review has done a literature search in databases of PubMed, Web of Science, China Science Periodical Database, and China National Knowledge Infrastructure for preclinical studies on PTL. The search terms used were \"Parthenolide\" and \"Nervous System Diseases\" as well as specific names of the diseases. We reviewed the mechanistic understanding on PTL of the available literature.</p><p><strong>Results: </strong>PTL inhibits the pathogenesis and development of neurological disease via a wide variety of mechanisms, such as an anti-inflammatory effect, an anti-oxidative stress effect, a reduction of neuronal apoptosis, and the relief of neuropathic pain. Since it addresses more than one pathway in the multifactorial pathological network of neurological illnesses, PTL may have synergistic or additive therapeutic benefits.</p><p><strong>Discussion: </strong>Multi-target therapeutic effects of PTL are effective in combating the interrelated pathological conditions of neurological disorders, whereas derivatives developed according to the structure-activity relationship (SAR) of PTL have additional potential to be clinically translated. Nevertheless, the existing data come mostly in the form of preclinical models, and their translation into clinical practice remains to be confirmed.</p><p><strong>Conclusion: </strong>PTL is a therapeutic agent with great promise in treating neurological disorders. Nevertheless, its potential as a translational drug also requires additional study and confirmation.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944067","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}