CNS & neurological disorders drug targets最新文献

{"title":"GFAP and UCHL1 in Non-traumatic SAH: The Story thus Far. A Systematic Review of the Literature.","authors":"Filippos Psochias, Georgios Mavrovounis, George Stranjalis, Theodosis Kalamatianos","doi":"10.2174/0118715273276472231116104549","DOIUrl":"10.2174/0118715273276472231116104549","url":null,"abstract":"<p><strong>Objective: </strong>Non-traumatic subarachnoid hemorrhage (SAH) is associated with a high percentage of misdiagnosis and poor prognosis. Biomarkers could be useful in the identification, treatment/management guidance, and outcome improvement of SAH patients. The current systematic review aims to investigate the potential role of biomarkers GFAP (Glial Fibrillary Acidic Protein) and UCH-L1 (Ubiquitin C-Terminal Hydrolase L1) in the diagnosis and prognosis of non-traumatic SAH.</p><p><strong>Methods: </strong>A systematic search of PubMed, Scopus, and Web of Science databases was conducted from their inception through February 2023.</p><p><strong>Results: </strong>17 studies met the inclusion criteria and were included in this review. The vast majority of the included studies (82%) were on GFAP. Most studies used blood and/or CSF samples and incorporated multiple measurements through the initial hospitalization days. The majority of identified studies reported significantly higher levels of GFAP and UCHL1 in SAH patients with poor outcomes. There was notable variation in the specimen type and the timing of sampling.</p><p><strong>Conclusion: </strong>Quantification of GFAP and UCHL1 through the initial days of hospitalization shows promise in the prediction of SAH patient outcomes. Further research is nevertheless warranted to confirm these findings and further clarify the use of the two biomarkers in SAH diagnosis and the prediction of severity and secondary events.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1328-1344"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428060","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":"Subarachnoid Hemorrhage.","authors":"Theodosis Kalamatianos","doi":"10.2174/187152732311240607222910","DOIUrl":"https://doi.org/10.2174/187152732311240607222910","url":null,"abstract":"","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":"23 11","pages":"1295-1296"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303475","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":"CRISPR/Cas9 Gene Editing: A Novel Approach Towards Alzheimer's Disease Treatment.","authors":"Siddhant Tripathi, Yashika Sharma, Rajesh Rane, Dileep Kumar","doi":"10.2174/0118715273283786240408034408","DOIUrl":"10.2174/0118715273283786240408034408","url":null,"abstract":"<p><p>In defiance of the vast amount of information regarding Alzheimer's disease (AD) that has been learned over the past thirty years, progress toward developing an effective therapy has been difficult. A neurological ailment that progresses and cannot be reversed is Alzheimer's disease, which shows neurofibrillary tangles, beta-amyloid plaque, and a lack of cognitive processes that is created by tau protein clumps with hyperphosphorylation that finally advances to neuronal damage without a recognized treatment, which has stimulated research into new therapeutic strategies. The protein CAS9 is linked to CRISPR, which is a clustered Regularly Interspaced Short Palindromic Repeat that inactivates or corrects a gene by recognizing a gene sequence that produces a doublestranded break has enchanted a whole amount of interest towards its potency to cure gene sequences in AD. The novel CRISPR-Cas9 applications for developing <i>in vitro</i> and <i>in vivo</i> models to the benefit of AD investigation and therapies are thoroughly analyzed in this work. The discussion will also touch on the creation of delivery methods, which is a significant obstacle to the therapeutic use of CRISPR/Cas9 technology. By concentrating on specific genes, such as those that are significant early- onset AD risk factors and late-onset AD risk factors, like the apolipoprotein E4 (APOE4) gene, this study aims to evaluate the potential application of CRISPR/Cas9 as a possible treatment for AD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1405-1424"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878178","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":"Analysis of Concentrations of Monomethyl Fumarate in Patients with Multiple Sclerosis: Result from Routine Health Care","authors":"Zuzana Krska Kusnirikova, Ivana Kacirova, Veronika Pesakova, Pavel Hradilek, Hana Brozmanova, Milan Grundmann","doi":"10.2174/0118715273302279240529104919","DOIUrl":"10.2174/0118715273302279240529104919","url":null,"abstract":"<p><strong>Background: </strong>Dimethyl fumarate is used to treat patients with relapsing-remitting multiple sclerosis. After ingestion, it is rapidly hydrolyzed to the active primary metabolite monomethyl fumarate.</p><p><strong>Objective: </strong>The main objective of our study was to analyze serum concentrations of monomethyl fumarate during routine health care in patients with multiple sclerosis treated with a fixed dose of dimethyl fumarate.</p><p><strong>Methods: </strong>In the pilot cross-sectional study, data from 42 patients treated with dimethyl fumarate at a dose of 240 mg twice daily were collected. Concentrations of the active metabolite monomethyl fumarate were determined at 1-8 h (median, 3 h) or 10-14 h (median, 13 h) after taking the dose. The relationship between monomethyl fumarate concentrations and absolute lymphocyte count was evaluated.</p><p><strong>Results: </strong>Concentrations of monomethyl fumarate ranged from 2.5-3177.9 μg/L, with most concentrations being undetectable approximately 10 hours after administration. In the 1-8 h (median, 3 h) post-dose subgroup, the concentration/dose ratio ranged widely from 0.04-6.62. The median concentration of monomethyl fumarate in the group with the absolute lymphocyte count <0.8 x 10^9/l was more than four times higher than in the group with the absolute lymphocyte count ≥0.8 x 10^9/l (median 440.1 μg/L versus 98.4 μg/L).</p><p><strong>Conclusion: </strong>The wide interindividual variability in monomethyl fumarate pharmacokinetics could contribute to the differential response to dimethyl fumarate in multiple sclerosis patients. A nonsignificant but noticeable trend was observed in the relationship of higher serum monomethyl fumarate concentrations to absolute lymphocyte counts.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1516 - 1523"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263462","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":"Food, Dietary Supplements and Nutraceuticals in Aging and Neurodegenerative Diseases.","authors":"Fabiola De Marchi, Giacomo Tondo","doi":"10.2174/187152732305231202011902","DOIUrl":"https://doi.org/10.2174/187152732305231202011902","url":null,"abstract":"","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":"23 5","pages":"543-544"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874379","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":"Anti-seizure Medications: Challenges and Opportunities.","authors":"Neha Tandon, Milica Radosavljevic, Danijela Vucevic, Miroslav Radenkovic, Jasna Jancic, Janko Samardzic","doi":"10.2174/0118715273275793231030060833","DOIUrl":"10.2174/0118715273275793231030060833","url":null,"abstract":"<p><p>Epilepsy is a chronic neurological condition characterized by unprovoked, recurrent seizures. There are several types of epilepsy, and the cause of the condition can vary. Some cases of epilepsy have a genetic component, while others may be caused by brain injuries, infections, or other underlying conditions. Treatment for epilepsy typically involves anti-seizure medications (ASMs), although different approaches, such as surgery or a special diet, may be considered in specific cases. The treatment aims to effectively manage and potentially eliminate seizures while minimizing any accompanying side effects. Many different ASMs are available, and the choice of medication depends on several factors, including the type of seizures, the patient's age, general health, and potential drug interactions. For the treatment of epilepsy, there have been significant advancements in recent decades, which have led to the approval of many different ASMs. Newer ASMs offer a broader range of mechanisms of action, improved tolerability profiles, and reduced drug interactions compared to older drugs. This review aims to discuss the pharmacological characteristics, clinical applications, effectiveness, and safety of ASMs, with a particular emphasis on various age groups, especially children. Moreover, this review seeks to provide a comprehensive understanding of ASM therapy for epilepsy management, assisting physicians in selecting suitable ASMs for their patients.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1120-1133"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405658","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":"LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.","authors":"Naser-Aldin Lashgari, Nazanin Momeni Roudsari, Amirhossein Niknejad, Hedieh Sadat Shamsnia, Maryam Shayan, Leila Mohaghegh Shalmani, Saeideh Momtaz, Nima Rezaei, Amir Hossein Abdolghaffari","doi":"10.2174/0118715273270874231205050727","DOIUrl":"10.2174/0118715273270874231205050727","url":null,"abstract":"<p><strong>Background: </strong>Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles.</p><p><strong>Objective: </strong>Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments.</p><p><strong>Method: </strong>English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022.</p><p><strong>Result: </strong>Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment.</p><p><strong>Conclusion: </strong>Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1177-1188"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567699","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":"Vasospasm in Pediatric Subarachnoid Hemorrhage.","authors":"Ioannis Mavridis, Efstratios-Stylianos Pyrgelis, Eleni Agapiou, Jeries Assi","doi":"10.2174/0118715273274147231104160152","DOIUrl":"10.2174/0118715273274147231104160152","url":null,"abstract":"<p><p>Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1303-1307"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138447539","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":"Memory Reflections of the Microbiota-Gut and Oligodendrocyte Axis.","authors":"Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/0118715273256132230921103333","DOIUrl":"10.2174/0118715273256132230921103333","url":null,"abstract":"<p><p>Memory is the persisting consequence of cognitive activities instigated by and engrossed on exterior information from the environment and commenced by an intensive on internal mental representations. Establishing a gut-brain axis (GBA) in health and disease has recently brought the gut, the main portal of communication with the external environment, to the forefront of this interaction. Dietary stimuli have long been linked to brain development, behavioral responses, and memory reflections. Vagus nerve, immune system, bacterial metabolites and products are just a few of the linkages that make up the GBA, a bidirectional arrangement of signaling pathways that connects the neurological system with the gastrointestinal tract. GBA involves two-way communication between central and enteric neural systems, connecting the brain's affective and cognitive regions to peripheral activities of the intestine. Recent scientific progress has highlighted the significance of gut microbiota in affecting these relationships. By controlling myelination at the prefrontal cortex, a crucial area for multifaceted cognitive behavior forecast and decision-making, this axis influences social behavior, including memory reflections. Humans may experience late myelination of the prefrontal cortex's axonal projections into the third decade of life, making it vulnerable to outside factors like microbial metabolites. It has been demonstrated that changes in the gut microbiome can change the microbial metabolome's composition, impacting highly permeable bioactive chemicals like p-cresol that may hinder oligodendrocyte differentiation. This review will discuss the memory reflections of the microbiota-gut and oligodendrocyte axis. Adopting this concept should encourage a new arena of thinking that recognizes the intricate central and periphery dynamics influencing behavior and uses that knowledge to develop novel therapies and interventions for maladjusted memory and learning systems.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"971-983"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686386","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":"Intrathecal Baclofen Infusion-Botulinum Toxin Combined Treatment Efficacy in the Management of Spasticity due to Cerebral Palsy.","authors":"Riccardo Marvulli, Giuseppa Lagioia, Giancarlo Ianieri, Lucrezia Dell'Olio, Alessandra Zonno, Mariagrazia Riccardi, Rosa Bianca Sinisi, Laura Belinda Rizzo, Giacomo Farì, Marisa Megna, Maurizio Ranieri","doi":"10.2174/0118715273250973230919121808","DOIUrl":"10.2174/0118715273250973230919121808","url":null,"abstract":"<p><strong>Background: </strong>Cerebral Palsy (CP) is a group of permanent, but not unchanging, disorders of movement and/or posture and motor function, which are due to a non-progressive interference, lesion, or abnormality of the developing/immature brain. One clinical presentation is muscle spasticity, which leads to a significant impact on the individual's functionality and quality of life. Spasticity treatment is multidisciplinary and includes pharmacological and physical intervention; intrathecal baclofen shows a positive effect in severe spasticity and suboptimal response to oral drugs, while local injection of Botulinum toxin type A (BTXA) improves muscle tone, motion and pain.</p><p><strong>Objective: </strong>The aim of this study was to evaluate the efficacy of the combined intrathecal baclofen infusion (ITB) - botulinum toxin treatment in the management of spasticity in CP.</p><p><strong>Methods: </strong>8 patients with spastic tetraparesis were enrolled. All patients were treated with intrathecal Baclofen; in lower limbs, no spastic symptoms appeared, while marked spasticity was noted in upper limbs. We injected the right and left Biceps Brachial (BB) and Flexor Digitorum Superficialis (FDS) muscles with botulinum toxin type A. All patients underwent Myometric measurement, Ashworth Scale, Numerical Rating Scale, and Visual Analogic Scale evaluation before infiltration (T0), 30 days after injection (T1), 60 days after injection (T2), and 90 days after treatment (T3).</p><p><strong>Results: </strong>All data demonstrated an improvement in spasticity, pain, quality of life, and self-care during the study, with p < 0.05. No side effects appeared.</p><p><strong>Conclusion: </strong>This study demonstrated the efficacy and safety of intrathecal baclofen infusion and botulinum toxin combined treatment in the management of spasticity, pain, quality of life, and selfcare in CP patients.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"917-926"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428061","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}