CNS & neurological disorders drug targets最新文献

{"title":"Targeting PPARs in the Brain: From Old Knowledge to Emerging Therapeutic Roles.","authors":"Alessandra Ammazzalorso","doi":"10.2174/0118715273387422250417185024","DOIUrl":"https://doi.org/10.2174/0118715273387422250417185024","url":null,"abstract":"","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056197","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":"Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.","authors":"Aditi Singh, Heena Khan, Amarjot Kaur Grewal, Kamal Dua, Sachin Kumar Singh, Thakur Gurjeet Singh","doi":"10.2174/0118715273377530250408212447","DOIUrl":"https://doi.org/10.2174/0118715273377530250408212447","url":null,"abstract":"<p><p>Opioid addiction is a condition of the central nervous system that occurs as a result of using opiate-based substances, which can be either natural or synthetic chemicals. These have effects identical to those of morphine and work by interacting with opioid receptors such as morphine, heroin, opium, buprenorphine, and Oxycontin. Dopamine has been suggested to play a role in the mechanisms linked to opioid addiction. Additionally, neurotransmitters such as serotonin, norepinephrine, glutamate, and GABA may also have a significant impact. These processes play a critical role in the formation of brain circuits that are involved in the development of addictive behavior. The PI3K-Akt-mTOR pathway is widely recognized as an essential regulator of the effects induced by neurotransmitters on synaptic plasticity, protein synthesis, and cellular responses. This interplay has considerable importance in the development and persistence of opioid addiction, impacting several domains, including reward processing, stress reactivity, and brain plasticity. The understanding of these neurochemical modifications provides vital insights into the underlying mechanisms of addiction and presents potential pathways for treatments. The review enlisted the clinical trials of different types of opioid addiction or dependence. The review offers a succinct summary of many studies that establish a correlation between the PI3K/Akt-mTOR signaling pathway and various receptors implicated in multiple forms of opioid-related dependency.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048192","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":"Exploring LRRK2-dependent Mechanisms in Parkinson's Disease Therapy.","authors":"Veerta Sharma, Shiwali Sharma, Shareen Singh, Thakur Gurjeet Singh","doi":"10.2174/0118715273377507250320035243","DOIUrl":"https://doi.org/10.2174/0118715273377507250320035243","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common progressive neurodegenerative disease worldwide and presents as a progressive motor disorder. Gene mutations play a pivotal role in the degeneration of dopaminergic neurons in the substantia nigra region. Mutations in the Leucine rich repeat kinase 2 (LRRK2) gene have been identified as one of the most common genetic causes of PD. LRRK2 is a multi-functional protein involved in several critical cellular processes, including mitochondrial function, autophagy, vesicular trafficking, and immune system regulation. Dysregulation of these processes due to aberrant LRRK2 activity contributes to neuronal degeneration, particularly in dopaminergic neurons, which are most affected in PD. The current review discusses the structure of LRRK2, its function, and pathogenic mutations in the context of PD. However, significant challenges remain, particularly in terms of ensuring drug specificity, minimizing off-target effects, and understanding the long-term safety and efficacy of these treatments. As we advance our understanding of LRRK2 biology, it remains a highly promising target for therapeutic strategies aimed at modifying the course of Parkinson's disease.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048756","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":"Neuroprotective Effect of Sitagliptin beyond the Incretin Effect: A Narrative Review.","authors":"Ali Mohammad Pourbagher-Shahri, Fatemeh Forouzanfar","doi":"10.2174/0118715273367858250321124131","DOIUrl":"https://doi.org/10.2174/0118715273367858250321124131","url":null,"abstract":"<p><p>Sitagliptin is a dipeptidyl peptidase-IV inhibitor approved for treating type 2 diabetes mellitus. It increases the active form of incretin Glucagon-like Peptide-1 (GLP-1). The GLP-1 peptide prevents damage to neurons due to its anti-inflammatory and anti-apoptotic activities. This article summarizes the studies assessing the neuroprotective properties of sitagliptin, especially through the GLP-1 pathway. The outcomes of experimental research indicate that sitagliptin has a decreasing effect on inflammation response. Sitagliptin decreases proinflammatory factors, such as Glial Fibrillary Acidic Protein (GFAP), Nuclear factor kappa B (NF-κB), Tumor Necrosis Factor-α (TNF- α), and Interleukin-6 (IL-6). It also decreases glutamate levels, the primary excitatory neurotransmitter. Furthermore, sitagliptin shows antioxidative and antiapoptotic effects. Lastly, sitagliptin may provide a novel agent for the management of neurological disease.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046398","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":"Molecular Interplay of ISG15/ISGylation in Neuropathologies.","authors":"Angeles C Tecalco-Cruz, Josué O Ramírez-Jarquín, Karen H Medina Abreu, Eva G Palacios-Serrato, Lilia López-Cánovas, Jesús Zepeda-Cervantes, Enrique Oropeza-Martínez","doi":"10.2174/0118715273378149250322050004","DOIUrl":"https://doi.org/10.2174/0118715273378149250322050004","url":null,"abstract":"<p><p>ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGylation. Research on protein ISGylation has increased in recent years, and some studies have suggested that ISG15 is involved in neuroprotection and neurodegeneration mechanisms. This review outlines the current state of research on the implications of ISG15/ISGylation in other neuropathies such as malignant tumors, ataxia telangiectasia, ischemia, depression, and neurodegenerative diseases such as Alzheimer´s, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neuroprotective effect when there is acute brain damage, but ISG15/ISGylation is associated with reduced neuroprotection when there is chronic damage, such as in neurodegenerative diseases.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058813","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":"Investigation and Mechanism of Coumarin for Potential Anti-Epileptic Targets using in-vitro SH-SY5Y Cell Line, Molecular Docking, and Network Pharmacology-based Analysis.","authors":"Khan Dureshahwar, Momin Saloni Taufique","doi":"10.2174/0118715273340950250315071352","DOIUrl":"https://doi.org/10.2174/0118715273340950250315071352","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Epilepsy affects 1-2% of the world population. In about 30% of individuals with epilepsy, the etiology is unknown after ruling out genetic mutations, severe injury, and several other possible causes. In about 20-30% of epilepsy patients, anti-epileptic drugs fail to control the seizures. The general trend in epilepsy genetics research is towards an increasingly powerful genetic platform for investigating genomic sequence and structural variation. This pattern will inevitably result in a quick rate of genetics-related discoveries and have significant effects on our capacity to identify and forecast epilepsy and related illnesses. About one-third of epileptic patients do not receive enough seizure control from the current medications. To close this treatment gap, new alternatives are required. Since phenytoin, a commercially available antiepileptic medicine, has a significant adverse effect called hypoguasia, which results in a diminished sense of taste, coumarin may lessen this side effect in addition to its antiepileptic properties, which are supported by several insilico and in-vitro studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The current study examined the potential anti-epileptic effects of coumarin using network pharmacology and in-vitro studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;During the initial stage, information about the phytoconstituent and the target genes linked to epilepsy and Coumarin was collected from open-source databases and scholarly literature. These data were then analyzed to identify common targets between the phytoconstituent and epilepsy. A Protein-Protein Interaction (PPI) network was built using the Search Tool for Identifying Interacting Genes and Proteins (STRING) database based on these common targets. Then, the hub genes were identified according to the degree of connectedness by integrating the Protein-Protein Interaction (PPI) network into the Cytoscape software. The networks of disease, genes, and Coumarin were obtained by following the processes of network pharmacology. A cell line investigation included the Cytotoxicity Study (MTT assay), Ca2+ Expression assay, and Mitochondrial Membrane Potential (JC-1 dye).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;In the intracellular Ca2+ expression assay, the intracellular Ca2+ rate was highly enhanced in the toxic group and moderately in the co-treatment of the poisonous and sample groups, suggesting the neuroprotective effect of coumarin-containing liposomes (Coumarosome) against the pentylenetetrazol (PTZ) induction on Epilepsy model. Also, a membrane potential dye (JC-1) ratio of pentylenetetrazol (PTZ)-treated cells was very low, 0.61 ± 0.12, whereas untreated cells showed a JC-1 ratio of 68.23 ± 36.37, respectively. It is suggested that coumarin-containing liposomes (Coumarosome) may have a better mitochondrial recovery rate. The evidence that this study exhibits antiepileptic activity comes from cell line research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/stron","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047238","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":"Cannabidiol from Conventional to Advanced Nanomedicines for the Management of Cancer-Associated Pain.","authors":"Abhishek Jain, Saba Qureshi, Km Rafiya, Irfan Ali, Mohd Shahrukh, Nazeer Hasan, Farhan Jalees Ahmad","doi":"10.2174/0118715273337554250311060327","DOIUrl":"https://doi.org/10.2174/0118715273337554250311060327","url":null,"abstract":"<p><p>Chemotherapy-induced pain is one of the major challenges that hamper the patient's quality of life. Several cases of insufficient pain management were reported globally, especially in the case of patients who do not respond well to conventional pain management regimes and opioid analgesics. Additionally, conventional pain management has several shortcomings, and evidence suggests that cannabidiol has the potential to overcome those shortcomings. Cannabidiol (CBD) is a non-psychoactive compound of the Cannabis plant that shows an effective outcome in chemotherapy- induced pain as well as in cancer treatment, as it possesses anti-inflammatory and analgesic properties. The mechanism of pain and its management by cannabidiol, with all possible evidence, is well summarised in the paper. This article concludes the types of pain experienced by cancer patients, the effectiveness of CBD in the management of pain, and challenges faced by patients after using Cannabidiol with various case studies. Later, antitumor efficacy studies of CBD were disclosed, and its various types of formulations and nano-formulations were summarized in the paper. Overall, the paper establishes the role of cannabidiol in Chemotherapy-induced pain.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733729","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":"Erythropoietin for Seizures and Epilepsy: Neuroprotective Effects, Mechanisms, and Contradictory Risks.","authors":"Heba M Mahdy","doi":"10.2174/0118715273367111250307081826","DOIUrl":"https://doi.org/10.2174/0118715273367111250307081826","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a widespread neurological disorder, particularly affecting children and the elderly, presenting complex and varied challenges in management. Recently, erythropoietin has gained significant attention due to its neuroprotective effects, which have been demonstrated experimentally in various neurological conditions, including epilepsy. This review aims to analyze current literature on the role of erythropoietin in seizures and epilepsy.</p><p><strong>Method: </strong>A comprehensive literature search was conducted through PubMed, Scopus, and Web of Science databases up to September 30, 2024. The search terms included \"Epilepsy AND Erythropoietin\", \"Seizures AND Erythropoietin,\" and \"Status Epilepticus AND Erythropoietin\", applied to titles, abstracts, and keywords.</p><p><strong>Results: </strong>The review highlights ongoing debates surrounding erythropoietin's effects on epilepsy. While erythropoietin shows potential in mitigating seizure-induced brain damage and modulating cellular processes such as anti-apoptotic and anti-inflammatory pathways, its clinical application is complicated by conflicting evidence. Some studies suggest that erythropoietin may trigger seizures, with factors such as dosage and individual patient characteristics potentially influencing this risk.</p><p><strong>Conclusion: </strong>Experimental studies suggest that erythropoietin offers neuroprotective benefits in epilepsy. However, its possible pro-convulsant effects-which might be linked to erythropoietin-induced hypertension, rapid increases in hematocrit levels, dosage, or individual patient characteristics-raise safety concerns. These risks complicate its clinical use, making it premature to endorse erythropoietin as a treatment fully. Future research should focus on non-erythropoietic derivatives that retain neuroprotective effects without stimulating red blood cell production, thereby reducing risks, such as hypertension and thrombosis. Well-designed clinical trials and further investigation into erythropoietin's mechanisms are essential to clarify its role and optimize its therapeutic potential in epilepsy.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733664","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":"Oxidative Stress and the Role of Immune Cells in Alzheimer's Disease: Therapeutic Implications and Future Perspectives.","authors":"Nidhi Puranik, Minseok Song","doi":"10.2174/0118715273355336250226055826","DOIUrl":"https://doi.org/10.2174/0118715273355336250226055826","url":null,"abstract":"<p><p>The most common neurodegenerative illness and leading cause of death in the world is Alzheimer's disease (AD), which is extremely expensive to treat. None of the AD treatments that are currently in the market with approval have any effect on disease progression. However, numerous clinical studies aimed at reducing amyloid beta (Aβ) plaque development, boosting Aβ clearance, or reducing neurofibrillary tangle (NFT) failed or had conflicting results. As oxidative stress (OS), mitochondrial dysfunction, and chronic neuroinflammation are implicated in numerous interconnected vicious cascades, research has revealed new therapeutic targets, including enhancing mitochondrial bioenergetics and quality control, reducing oxidative stress, or modulating neuroinflammatory pathways. This review examines the role of oxidative stress (OS), mitochondrial dysfunction, neuroinflammation, and the interplay between peripheral and central immune systems in the pathogenesis of AD. We highlight how OS and immune dysregulation drive chronic neuroinflammation, exacerbating AD progression. Immune cells and inflammatory molecules emerge as critical players in disease pathology. Overall, this review concludes that targeting OS and immune system crosstalk represents promising therapeutic strategies for mitigating AD progression, providing a foundation for future interventions.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671990","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":"Lithium Chloride Rescues Dopaminergic Neurons in a Parkinson's Disease Rat Model Challenged with Rotenone.","authors":"Eman Allam, Sary Khalil Abdel Ghafar, Manal Hussein, Ahmed Al-Emam, Khaled Radad","doi":"10.2174/0118715273365449250224090655","DOIUrl":"https://doi.org/10.2174/0118715273365449250224090655","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease, the second most common neurodegenerative disease, is still lacking an effective treatment that can stop dopaminergic cell loss in substantia nigra and alter disease progression.</p><p><strong>Objective: </strong>The present study aimed to investigate the neuroprotective efficacy of lithium chloride in a rotenone-induced rat model of Parkinson's disease.</p><p><strong>Methods: </strong>Forty male Sprague Dawley rats were assigned into 4 groups: control, rotenone-, rotenone and lithium chloride- and lithium chloride-treated groups. Rotenone (2 mg/kg b.w.) and lithium chloride (60 mg/kg b.w.) were, respectively, administered subcutaneously and orally five times a week for 5 weeks. At the end of each treatment, the neuroprotective efficacy of lithium chloride against rotenone-induced derangements was evaluated by some behavioral tests, biochemical analysis, gel electrophoresis, histopathology, and immunohistochemistry.</p><p><strong>Results: </strong>Rotenone significantly resulted in neurobehavioral deficits, gastrointestinal dysfunction, decreased activities of catalase and superoxide dismutase, depleted glutathione, and increased levels of malondialdehyde. It also caused DNA fragmentation and loss of dopaminergic neurons in substantia nigra and decreased striatal tyrosine hydroxylase staining intensity. Concomitant treatment of rats with rotenone and lithium chloride significantly improved behavioral impairment and markedly alleviated gastrointestinal dysfunction. It also increased catalase activity and decreased malondialdehyde levels, indicating antioxidant effects. Moreover, it decreased DNA fragmentation, rescued dopaminergic neurons, and increased tyrosine hydroxylase immunoreactivity in the striatum compared to the rotenone-treated group.</p><p><strong>Conclusion: </strong>Lithium chloride rescued dopaminergic neurons in a rotenone model of PD, possibly through the improvement of behavioral deficits, decreasing oxidative stress, and reducing DNA damage.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671987","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}