Pub Date : 2024-01-01DOI: 10.2174/0118715273275793231030060833
Neha Tandon, Milica Radosavljevic, Danijela Vucevic, Miroslav Radenkovic, Jasna Jancic, Janko Samardzic
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.
{"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":null,"pages":null},"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}
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 in vitro and in vivo 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.
尽管过去三十年来人们了解了大量有关阿尔茨海默病(AD)的信息,但在开发有效疗法方面却一直举步维艰。阿尔茨海默病是一种进展缓慢且无法逆转的神经系统疾病,它表现为神经纤维缠结、β-淀粉样蛋白斑块和认知过程缺失,而认知过程缺失是由具有高磷酸化的 tau 蛋白团块造成的,最终发展为神经元损伤,却没有公认的治疗方法,这激发了人们对新治疗策略的研究。CAS9蛋白与CRISPR相关联,CRISPR是一种簇状正则间隔短回文重复序列(clustered Regularly Interspaced Short Palindromic Repeat),它通过识别产生双链断裂的基因序列来使基因失活或纠正基因。本研究将深入分析 CRISPR-Cas9 在开发体外和体内模型方面的新应用,以促进 AD 研究和治疗。讨论还将涉及传递方法的创建,这是 CRISPR/Cas9 技术用于治疗的一个重大障碍。通过集中研究特定基因,如那些重要的早发性AD风险因素和晚发性AD风险因素,如载脂蛋白E4(APOE4)基因,本研究旨在评估CRISPR/Cas9作为一种可能的AD治疗方法的潜在应用。
{"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":null,"pages":null},"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}
Pub Date : 2024-01-01DOI: 10.2174/0118715273302279240529104919
Zuzana Krska Kusnirikova, Ivana Kacirova, Veronika Pesakova, Pavel Hradilek, Hana Brozmanova, Milan Grundmann
Background: 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.
Objective: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
{"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":null,"pages":null},"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}
Background: 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.
Objective: 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.
Methods: 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).
Results: 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.
Conclusion: 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-01-01DOI: 10.2174/0118715273258337230925040049
Bhavana Yerraguravagari, Naga Pavani Penchikala, Aravinda Sai Kolusu, Grandhi Sandeep Ganesh, Prasad Konduri, Kumar V S Nemmani, Pavan Kumar Samudrala
Background: Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders.
Objective: This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation.
Methods: Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect.
Results: Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05).
Conclusion: Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels.
{"title":"Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF.","authors":"Bhavana Yerraguravagari, Naga Pavani Penchikala, Aravinda Sai Kolusu, Grandhi Sandeep Ganesh, Prasad Konduri, Kumar V S Nemmani, Pavan Kumar Samudrala","doi":"10.2174/0118715273258337230925040049","DOIUrl":"10.2174/0118715273258337230925040049","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders.</p><p><strong>Objective: </strong>This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation.</p><p><strong>Methods: </strong>Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect.</p><p><strong>Results: </strong>Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05).</p><p><strong>Conclusion: </strong>Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41174146","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}
Pub Date : 2024-01-01DOI: 10.2174/0118715273277458231213063147
Seyed Hossein Shahcheraghi, Elmira Roshani Asl, Malihe Lotfi, Jamshid Ayatollahi, Seyed Hossein Khaleghinejad, Alaa A A Aljabali, Hamid A Bakshi, Mohamed El-Tanani, Nitin B Charbe, Ángel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Rohit Goyal, Altijana Hromić-Jahjefendić, Vladimir N Uversky, Marzieh Lotfi, Murtaza M Tambuwala
Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.
{"title":"Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets.","authors":"Seyed Hossein Shahcheraghi, Elmira Roshani Asl, Malihe Lotfi, Jamshid Ayatollahi, Seyed Hossein Khaleghinejad, Alaa A A Aljabali, Hamid A Bakshi, Mohamed El-Tanani, Nitin B Charbe, Ángel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Rohit Goyal, Altijana Hromić-Jahjefendić, Vladimir N Uversky, Marzieh Lotfi, Murtaza M Tambuwala","doi":"10.2174/0118715273277458231213063147","DOIUrl":"10.2174/0118715273277458231213063147","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567700","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}
Pub Date : 2024-01-01DOI: 10.2174/0118715273280701231227100805
Samah Kandeel, Marwa M Abd-Elsalam, Sherief Abd-Elsalam, Heba Hassan Elkaliny
Introduction: Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions.
Aim: This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods.
Methods: 35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100 mg/kg/day and BPH (100 mg/kg/ three times/week).
Results: BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase- 3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results.
Conclusion: Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.
{"title":"The Possible Protective Effect of Taurine on Bisphenol Induced Structural Changes on the Cerebral Cortex of Rats: Histological and Immunohistochemical Study.","authors":"Samah Kandeel, Marwa M Abd-Elsalam, Sherief Abd-Elsalam, Heba Hassan Elkaliny","doi":"10.2174/0118715273280701231227100805","DOIUrl":"10.2174/0118715273280701231227100805","url":null,"abstract":"<p><strong>Introduction: </strong>Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions.</p><p><strong>Aim: </strong>This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods.</p><p><strong>Methods: </strong>35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100 mg/kg/day and BPH (100 mg/kg/ three times/week).</p><p><strong>Results: </strong>BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase- 3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results.</p><p><strong>Conclusion: </strong>Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652450","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}
Pub Date : 2024-01-01DOI: 10.2174/0118715273256132230921103333
Suman Kumar Ray, Sukhes Mukherjee
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.
{"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":null,"pages":null},"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}
Background: 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.
Objective: 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.
Method: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022.
Result: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment.
Conclusion: 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-01-01DOI: 10.2174/0118715273274147231104160152
Ioannis Mavridis, Efstratios-Stylianos Pyrgelis, Eleni Agapiou, Jeries Assi
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.
{"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":null,"pages":null},"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}