Pub Date : 2024-01-01DOI: 10.2174/1871527322666230406094257
Yolanda Santiago-Vicente, Manuel de Jesús Castillejos-López, Liliana Carmona-Aparicio, Elvia Coballase-Urrutia, Liliana Velasco-Hidalgo, Ana María Niembro-Zúñiga, Marta Zapata-Tarrés, Luz María Torres-Espíndola
Background: B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer.
Objective: This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients.
Results: Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success.
Conclusion: Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.
{"title":"Immunotherapy for Pediatric Gliomas: CAR-T Cells Against B7H3: A Review of the Literature.","authors":"Yolanda Santiago-Vicente, Manuel de Jesús Castillejos-López, Liliana Carmona-Aparicio, Elvia Coballase-Urrutia, Liliana Velasco-Hidalgo, Ana María Niembro-Zúñiga, Marta Zapata-Tarrés, Luz María Torres-Espíndola","doi":"10.2174/1871527322666230406094257","DOIUrl":"10.2174/1871527322666230406094257","url":null,"abstract":"<p><strong>Background: </strong>B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer.</p><p><strong>Objective: </strong>This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients.</p><p><strong>Results: </strong>Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success.</p><p><strong>Conclusion: </strong>Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230515155000
Athulya Krishna, Sunil Kumar, Sachithra Thazhathuveedu Sudevan, Ashutosh Kumar Singh, Leena K Pappachen, T M Rangarajan, Mohamed A Abdelgawad, Bijo Mathew
Monoamine oxidase B is a crucial therapeutic target for neurodegenerative disorders like Alzheimer's and Parkinson's since they assist in disintegrating neurotransmitters such as dopamine in the brain. Pursuing efficacious monoamine oxidase B inhibitors is a hot topic, as contemporary therapeutic interventions have many shortcomings. Currently available FDA-approved monoamine oxidase inhibitors like safinamide, selegiline and rasagiline also have a variety of side effects like depression and insomnia. In the quest for a potent monoamine oxidase B inhibitor, sizeable, diverse chemical entities have been uncovered, including chalcones. Chalcone is a renowned structural framework that has been intensively explored for its monoamine oxidase B inhibitory activity.The structural resemblance of chalcone (1,3-diphenyl-2-propen-1-one) based compounds and 1,4-diphenyl- 2-butene, a recognized MAO-B inhibitor, accounts for their MAO-B inhibitory activity. Therefore, multiple revisions to the chalcone scaffold have been attempted by the researchers to scrutinize the implications of substitutions onthe molecule's potency. In this work, we outline the docking investigation results of various chalcone analogues with monoamine oxidase B available in the literature until now to understand the interaction modes and influence of substituents. Here we focused on the interactions between reported chalcone derivatives and the active site of monoamine oxidase B and the influence of substitutions on those interactions. Detailed images illustrating the interactions and impact of the substituents or structural modifications on these interactions were used to support the docking results.
单胺氧化酶 B 是阿尔茨海默氏症和帕金森氏症等神经退行性疾病的重要治疗靶点,因为它们能帮助分解大脑中的多巴胺等神经递质。由于当代治疗干预措施存在许多缺陷,因此寻找有效的单胺氧化酶 B 抑制剂是一个热门话题。目前美国食品及药物管理局(FDA)批准的单胺氧化酶抑制剂,如沙芬胺、西格列汀和拉沙吉林,也有各种副作用,如抑郁和失眠。在寻找强效单胺氧化酶 B 抑制剂的过程中,人们发现了大量不同的化学实体,其中包括查耳酮。基于查尔酮(1,3-二苯基-2-丙烯-1-酮)的化合物和 1,4-二苯基-2-丁烯(一种公认的 MAO-B 抑制剂)在结构上的相似性是它们具有 MAO-B 抑制活性的原因。因此,研究人员对查尔酮支架进行了多次修改,以仔细研究取代对分子效力的影响。在这项工作中,我们概述了迄今为止文献中各种查尔酮类似物与单胺氧化酶 B 的对接研究结果,以了解取代基的相互作用模式和影响。在这里,我们重点研究了已报道的查尔酮衍生物与单胺氧化酶 B 活性位点之间的相互作用以及取代基对这些相互作用的影响。为了支持对接结果,我们使用了详细的图像来说明相互作用以及取代基或结构修饰对这些相互作用的影响。
{"title":"A Comprehensive Review of the Docking Studies of Chalcone for the Development of Selective MAO-B Inhibitors.","authors":"Athulya Krishna, Sunil Kumar, Sachithra Thazhathuveedu Sudevan, Ashutosh Kumar Singh, Leena K Pappachen, T M Rangarajan, Mohamed A Abdelgawad, Bijo Mathew","doi":"10.2174/1871527322666230515155000","DOIUrl":"10.2174/1871527322666230515155000","url":null,"abstract":"<p><p>Monoamine oxidase B is a crucial therapeutic target for neurodegenerative disorders like Alzheimer's and Parkinson's since they assist in disintegrating neurotransmitters such as dopamine in the brain. Pursuing efficacious monoamine oxidase B inhibitors is a hot topic, as contemporary therapeutic interventions have many shortcomings. Currently available FDA-approved monoamine oxidase inhibitors like safinamide, selegiline and rasagiline also have a variety of side effects like depression and insomnia. In the quest for a potent monoamine oxidase B inhibitor, sizeable, diverse chemical entities have been uncovered, including chalcones. Chalcone is a renowned structural framework that has been intensively explored for its monoamine oxidase B inhibitory activity.The structural resemblance of chalcone (1,3-diphenyl-2-propen-1-one) based compounds and 1,4-diphenyl- 2-butene, a recognized MAO-B inhibitor, accounts for their MAO-B inhibitory activity. Therefore, multiple revisions to the chalcone scaffold have been attempted by the researchers to scrutinize the implications of substitutions onthe molecule's potency. In this work, we outline the docking investigation results of various chalcone analogues with monoamine oxidase B available in the literature until now to understand the interaction modes and influence of substituents. Here we focused on the interactions between reported chalcone derivatives and the active site of monoamine oxidase B and the influence of substitutions on those interactions. Detailed images illustrating the interactions and impact of the substituents or structural modifications on these interactions were used to support the docking results.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230501232815
Aditya Singh, Vaseem Ahamad Ansari, Tarique Mahmood, Farogh Ahsan, Rufaida Wasim, Shubhrat Maheshwari, Mohammad Shariq, Saba Parveen, Arshiya Shamim
Nanotechnology is a great choice for medical research, and the green synthesis approach is a novel and better way to synthesize nanoparticles. Biological sources are cost-effective, environmentally friendly, and allow large-scale production of nanoparticles. Naturally obtained 3 β-hydroxy-urs- 12-en-28-oic acids reported for neuroprotective and dendritic structure are reported as solubility enhancers. Plants are free from toxic substances and act as natural capping agents. In this review, the pharmacological properties of ursolic acid (UA) and the structural properties of the dendritic structure are discussed. UA acid appears to have negligible toxicity and immunogenicity, as well as favorable biodistribution, according to the current study, and the dendritic structure improves drug solubility, prevents drug degradation, increases circulation time, and potentially targets by using different pathways with different routes of administration. Nanotechnology is a field in which materials are synthesized at the nanoscale. Nanotechnology could be the next frontier of humankind's technological advancement. Richard Feynman first used the term 'Nanotechnology' in his lecture, "There is Plenty of Room at the Bottom", on 29th December, 1959, and since then, interest has increased in the research on nanoparticles. Nanotechnology is capable of helping humanity by solving major challenges, particularly in neurological disorders like Alzheimer's disease (AD), the most prevalent type, which may account for 60-70% of cases. Other significant forms of dementia include vascular dementia, dementia with Lewy bodies (abnormal protein aggregates that form inside nerve cells), and a number of illnesses that exacerbate frontotemporal dementia. Dementia is an acquired loss of cognition in several cognitive domains that are severe enough to interfere with social or professional functioning. However, dementia frequently co-occurs with other neuropathologies, typically AD with cerebrovascular dysfunction. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some neurons. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders cause cognitive impairment and dementia, and as average life expectancy rises globally, their effects become more noticeable.
纳米技术是医学研究的最佳选择,而绿色合成法是合成纳米粒子的一种新颖、更好的方法。生物资源具有成本低、环境友好等特点,可以大规模生产纳米粒子。据报道,天然获得的 3 β-hydroxy-urs- 12-en-28-oic acids 具有神经保护和树突结构的作用,可作为溶解性增强剂。植物不含有毒物质,是天然的封顶剂。本综述讨论了熊果酸(UA)的药理特性和树突结构特性。根据目前的研究,熊果酸的毒性和免疫原性几乎可以忽略不计,而且具有良好的生物分布,树枝状结构可提高药物的溶解度,防止药物降解,延长循环时间,并可通过不同的给药途径发挥潜在的靶向作用。纳米技术是在纳米尺度上合成材料的领域。纳米技术可能是人类技术进步的下一个前沿领域。理查德-费曼(Richard Feynman)在 1959 年 12 月 29 日的演讲 "There is Plenty of Room at the Bottom "中首次使用了 "纳米技术 "一词,此后,人们对纳米粒子研究的兴趣与日俱增。纳米技术能够帮助人类解决重大挑战,特别是神经系统疾病,如阿尔茨海默病(AD),这是一种最常见的疾病,可能占病例的 60-70%。其他重要的痴呆形式包括血管性痴呆、路易体痴呆(神经细胞内形成的异常蛋白质聚集体),以及一些会加重额颞叶痴呆的疾病。痴呆症是一种后天性认知能力丧失,涉及多个认知领域,严重程度足以影响社会或职业功能。然而,痴呆症经常与其他神经病理学并发,典型的是伴有脑血管功能障碍的注意力缺失症。临床表现显示,神经退行性疾病通常无法治愈,因为患者会永久性地失去部分神经元。越来越多的研究表明,这些疾病也增进了我们对维持大脑健康和功能的关键过程的了解。严重的神经功能损伤和神经元死亡是神经退行性疾病的主要特征,也是极其严重的致残性疾病。最常见的神经退行性疾病会导致认知障碍和痴呆症,随着全球平均寿命的延长,这些疾病的影响也越来越明显。
{"title":"Emerging Nanotechnology for the Treatment of Alzheimer's Disease.","authors":"Aditya Singh, Vaseem Ahamad Ansari, Tarique Mahmood, Farogh Ahsan, Rufaida Wasim, Shubhrat Maheshwari, Mohammad Shariq, Saba Parveen, Arshiya Shamim","doi":"10.2174/1871527322666230501232815","DOIUrl":"10.2174/1871527322666230501232815","url":null,"abstract":"<p><p>Nanotechnology is a great choice for medical research, and the green synthesis approach is a novel and better way to synthesize nanoparticles. Biological sources are cost-effective, environmentally friendly, and allow large-scale production of nanoparticles. Naturally obtained 3 β-hydroxy-urs- 12-en-28-oic acids reported for neuroprotective and dendritic structure are reported as solubility enhancers. Plants are free from toxic substances and act as natural capping agents. In this review, the pharmacological properties of ursolic acid (UA) and the structural properties of the dendritic structure are discussed. UA acid appears to have negligible toxicity and immunogenicity, as well as favorable biodistribution, according to the current study, and the dendritic structure improves drug solubility, prevents drug degradation, increases circulation time, and potentially targets by using different pathways with different routes of administration. Nanotechnology is a field in which materials are synthesized at the nanoscale. Nanotechnology could be the next frontier of humankind's technological advancement. Richard Feynman first used the term 'Nanotechnology' in his lecture, \"There is Plenty of Room at the Bottom\", on 29th December, 1959, and since then, interest has increased in the research on nanoparticles. Nanotechnology is capable of helping humanity by solving major challenges, particularly in neurological disorders like Alzheimer's disease (AD), the most prevalent type, which may account for 60-70% of cases. Other significant forms of dementia include vascular dementia, dementia with Lewy bodies (abnormal protein aggregates that form inside nerve cells), and a number of illnesses that exacerbate frontotemporal dementia. Dementia is an acquired loss of cognition in several cognitive domains that are severe enough to interfere with social or professional functioning. However, dementia frequently co-occurs with other neuropathologies, typically AD with cerebrovascular dysfunction. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some neurons. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders cause cognitive impairment and dementia, and as average life expectancy rises globally, their effects become more noticeable.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9405257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230519113201
Othman Saleh, Khaled Albakri, Abdalrahmn Altiti, Iser Abutair, Suhaib Shalan, Omar Bassam Mohd, Ahmed Negida, Gohar Mushtaq, Mohammad A Kamal
Long non-coding RNAs (IncRNAs) are regulatory RNA transcripts that have recently been associated with the onset of many neurodegenerative illnesses, including Alzheimer's disease (AD). Several IncRNAs have been found to be associated with AD pathophysiology, each with a distinct mechanism. In this review, we focused on the role of IncRNAs in the pathogenesis of AD and their potential as novel biomarkers and therapeutic targets. Searching for relevant articles was done using the PubMed and Cochrane library databases. Studies had to be published in full text in English in order to be considered. Some IncRNAs were found to be upregulated, while others were downregulated. Dysregulation of IncRNAs expression may contribute to AD pathogenesis. Their effects manifest as the synthesis of beta-amyloid (Aβ) plaques increases, thereby altering neuronal plasticity, inducing inflammation, and promoting apoptosis. Despite the need for more investigations, IncRNAs could potentially increase the sensitivity of early detection of AD. Until now, there has been no effective treatment for AD. Hence, InRNAs are promising molecules and may serve as potential therapeutic targets. Although several dysregulated AD-associated lncRNAs have been discovered, the functional characterization of most lncRNAs is still lacking.
{"title":"The Role of Non-coding RNAs in Alzheimer's Disease: Pathogenesis, Novel Biomarkers, and Potential Therapeutic Targets.","authors":"Othman Saleh, Khaled Albakri, Abdalrahmn Altiti, Iser Abutair, Suhaib Shalan, Omar Bassam Mohd, Ahmed Negida, Gohar Mushtaq, Mohammad A Kamal","doi":"10.2174/1871527322666230519113201","DOIUrl":"10.2174/1871527322666230519113201","url":null,"abstract":"<p><p>Long non-coding RNAs (IncRNAs) are regulatory RNA transcripts that have recently been associated with the onset of many neurodegenerative illnesses, including Alzheimer's disease (AD). Several IncRNAs have been found to be associated with AD pathophysiology, each with a distinct mechanism. In this review, we focused on the role of IncRNAs in the pathogenesis of AD and their potential as novel biomarkers and therapeutic targets. Searching for relevant articles was done using the PubMed and Cochrane library databases. Studies had to be published in full text in English in order to be considered. Some IncRNAs were found to be upregulated, while others were downregulated. Dysregulation of IncRNAs expression may contribute to AD pathogenesis. Their effects manifest as the synthesis of beta-amyloid (Aβ) plaques increases, thereby altering neuronal plasticity, inducing inflammation, and promoting apoptosis. Despite the need for more investigations, IncRNAs could potentially increase the sensitivity of early detection of AD. Until now, there has been no effective treatment for AD. Hence, InRNAs are promising molecules and may serve as potential therapeutic targets. Although several dysregulated AD-associated lncRNAs have been discovered, the functional characterization of most lncRNAs is still lacking.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9746895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230303114425
Gunel Ayyubova
Alzheimer's disease (AD) is a progressive neurodegenerative disease, the main pathological hallmark of which is the loss of neurons, resulting in cognitive and memory impairments. Sporadic late-onset AD is a prevalent form of the disease and the apolipoprotein E4 (APOE4) genotype is the strongest predictor of the disease development. The structural variations of APOE isoforms affect their roles in synaptic maintenance, lipid trafficking, energy metabolism, inflammatory response, and BBB integrity. In the context of AD, APOE isoforms variously control the key pathological elements of the disease, including Aβ plaque formation, tau aggregation, and neuroinflammation. Taking into consideration the limited number of therapy choices that can alleviate symptoms and have little impact on the AD etiology and progression to date, the precise research strategies guided by apolipoprotein E (APOE) polymorphisms are required to assess the potential risk of age-related cognitive decline in people carrying APOE4 genotype. In this review, we summarize the evidence implicating the significance of APOE isoforms on brain functions in health and pathology with the aim to identify the possible targets that should be addressed to prevent AD manifestation in individuals with the APOE4 genotype and to explore proper treatment strategies.
{"title":"APOE4 is a Risk Factor and Potential Therapeutic Target for Alzheimer's Disease.","authors":"Gunel Ayyubova","doi":"10.2174/1871527322666230303114425","DOIUrl":"10.2174/1871527322666230303114425","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease, the main pathological hallmark of which is the loss of neurons, resulting in cognitive and memory impairments. Sporadic late-onset AD is a prevalent form of the disease and the apolipoprotein E4 (APOE4) genotype is the strongest predictor of the disease development. The structural variations of APOE isoforms affect their roles in synaptic maintenance, lipid trafficking, energy metabolism, inflammatory response, and BBB integrity. In the context of AD, APOE isoforms variously control the key pathological elements of the disease, including Aβ plaque formation, tau aggregation, and neuroinflammation. Taking into consideration the limited number of therapy choices that can alleviate symptoms and have little impact on the AD etiology and progression to date, the precise research strategies guided by apolipoprotein E (APOE) polymorphisms are required to assess the potential risk of age-related cognitive decline in people carrying APOE4 genotype. In this review, we summarize the evidence implicating the significance of APOE isoforms on brain functions in health and pathology with the aim to identify the possible targets that should be addressed to prevent AD manifestation in individuals with the APOE4 genotype and to explore proper treatment strategies.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10828597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230627123426
Sushma Singh, Neetu Agrawal, Ahsas Goyal
Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions worldwide. One of the leading hypotheses for the underlying cause of AD is a reduction in nicotinic receptor levels in the brain. Among the nicotinic receptors, the alpha-7-nicotinic acetylcholine receptor (α7nAChR) has received particular attention due to its involvement in cognitive function.α7nAChR is a ligand-gated ion channel that is primarily found in the hippocampus and prefrontal cortex, areas of the brain responsible for learning, memory, and attention. Studies have shown that α7nAChR dysfunction is a key contributor to the pathogenesis of AD. The receptor is involved in regulating amyloidbeta (Aβ) production, a hallmark of AD pathology. Many drugs have been investigated as α7nAChR agonists or allosteric modulators to improve cognitive deficits in AD. Clinical studies have shown promising results with α7nAChR agonists, including improved memory and cognitive function. Although several studies have shown the significance of the α7 nAChR in AD, little is known about its function in AD pathogenesis. As a result, in this review, we have outlined the basic information of the α7 nAChR's structure, functions, cellular responses to its activation, and its role in AD's pathogenesis.
{"title":"Role of Alpha-7-Nicotinic Acetylcholine Receptor in Alzheimer's Disease.","authors":"Sushma Singh, Neetu Agrawal, Ahsas Goyal","doi":"10.2174/1871527322666230627123426","DOIUrl":"10.2174/1871527322666230627123426","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions worldwide. One of the leading hypotheses for the underlying cause of AD is a reduction in nicotinic receptor levels in the brain. Among the nicotinic receptors, the alpha-7-nicotinic acetylcholine receptor (α7nAChR) has received particular attention due to its involvement in cognitive function.α7nAChR is a ligand-gated ion channel that is primarily found in the hippocampus and prefrontal cortex, areas of the brain responsible for learning, memory, and attention. Studies have shown that α7nAChR dysfunction is a key contributor to the pathogenesis of AD. The receptor is involved in regulating amyloidbeta (Aβ) production, a hallmark of AD pathology. Many drugs have been investigated as α7nAChR agonists or allosteric modulators to improve cognitive deficits in AD. Clinical studies have shown promising results with α7nAChR agonists, including improved memory and cognitive function. Although several studies have shown the significance of the α7 nAChR in AD, little is known about its function in AD pathogenesis. As a result, in this review, we have outlined the basic information of the α7 nAChR's structure, functions, cellular responses to its activation, and its role in AD's pathogenesis.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10063919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230619103429
Hammad Riaz, Mohammad Uzair, Muhammad Arshad, Ali Hamza, Nedal Bukhari, Faisal Azam, Shahid Bashir
Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for analyzing the central and peripheral nervous system. TMS could be a powerful therapeutic technique for neurological disorders. TMS has also shown potential in treating various neurophysiological complications, such as depression, anxiety, and obsessive-compulsive disorders, without pain and analgesics. Despite advancements in diagnosis and treatment, there has been an increase in the prevalence of brain cancer globally. For surgical planning, mapping brain tumors has proven challenging, particularly those localized in expressive regions. Preoperative brain tumor mapping may lower the possibility of postoperative morbidity in surrounding areas. A navigated TMS (nTMS) uses magnetic resonance imaging (MRI) to enable precise mapping during navigated brain stimulation. The resulting magnetic impulses can be precisely applied to the target spot in the cortical region by employing nTMS. This review focuses on nTMS for preoperative planning for brain cancer. This study reviews several studies on TMS and its subtypes in treating cancer and surgical planning. nTMS gives wider and improved dimensions of preoperative planning of the motor-eloquent areas in brain tumor patients. nTMS also predicts postoperative neurological deficits, which might be helpful in counseling patients. nTMS have the potential for finding possible abnormalities in the motor cortex areas.
{"title":"Navigated Transcranial Magnetic Stimulation (nTMS) based Preoperative Planning for Brain Tumor Treatment.","authors":"Hammad Riaz, Mohammad Uzair, Muhammad Arshad, Ali Hamza, Nedal Bukhari, Faisal Azam, Shahid Bashir","doi":"10.2174/1871527322666230619103429","DOIUrl":"10.2174/1871527322666230619103429","url":null,"abstract":"<p><p>Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for analyzing the central and peripheral nervous system. TMS could be a powerful therapeutic technique for neurological disorders. TMS has also shown potential in treating various neurophysiological complications, such as depression, anxiety, and obsessive-compulsive disorders, without pain and analgesics. Despite advancements in diagnosis and treatment, there has been an increase in the prevalence of brain cancer globally. For surgical planning, mapping brain tumors has proven challenging, particularly those localized in expressive regions. Preoperative brain tumor mapping may lower the possibility of postoperative morbidity in surrounding areas. A navigated TMS (nTMS) uses magnetic resonance imaging (MRI) to enable precise mapping during navigated brain stimulation. The resulting magnetic impulses can be precisely applied to the target spot in the cortical region by employing nTMS. This review focuses on nTMS for preoperative planning for brain cancer. This study reviews several studies on TMS and its subtypes in treating cancer and surgical planning. nTMS gives wider and improved dimensions of preoperative planning of the motor-eloquent areas in brain tumor patients. nTMS also predicts postoperative neurological deficits, which might be helpful in counseling patients. nTMS have the potential for finding possible abnormalities in the motor cortex areas.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypovolemic shock (HS), a clinical condition of insufficient blood perfusion and oxygenation in body tissues, is associated with immense morbidity and mortality. Treatment approaches include fluid replacement and surgical repair of reversible causes of hemorrhage; however, they cause irreversible blood perfusion loss, systemic inflammation, multiple organ failure, and death. Centhaquin citrate (CC) is an innovative centrally acting cardiovascular active agent that is initially intended as an antihypertensive drug. However, due to its positive ionotropic effect, Centhaquin citrate is being tested clinically as a resuscitative agent for the management of hypovolemic shock It acts at the α2B-adrenergic receptor to produce venous constriction followed by an increase in venous return to the heart. These actions are assumed to be capable of resuscitative activity observed by centhaquin citrate, through an increase in cardiac output and tissue perfusion. Pharmacokinetics investigations in animals and humans have shown that centhaquin citrate is well tolerated and has insignificant side effects. Therefore, centhaquin citrate seems to be a promising entity and gaining the interest of researchers to develop it as a resuscitative agent in HS. The review gives insight into the development of centhaquin citrate as a resuscitative agent and provides insight into the associated mechanism of action and molecular signalling to foster future research on CC for its clinical use in HS.
{"title":"Evolutionary Unmasking Resuscitative Therapeutics Potential of Centhaquin Citrate in Hypovolemic Shock.","authors":"Ravinder Singh, Varinder Singh, Pratima Kumari, Namita Aggarwal, Muskaan Oberoi, Heena Khan, Thakur Gurjeet Singh","doi":"10.2174/1871527322666230623113013","DOIUrl":"10.2174/1871527322666230623113013","url":null,"abstract":"<p><p>Hypovolemic shock (HS), a clinical condition of insufficient blood perfusion and oxygenation in body tissues, is associated with immense morbidity and mortality. Treatment approaches include fluid replacement and surgical repair of reversible causes of hemorrhage; however, they cause irreversible blood perfusion loss, systemic inflammation, multiple organ failure, and death. Centhaquin citrate (CC) is an innovative centrally acting cardiovascular active agent that is initially intended as an antihypertensive drug. However, due to its positive ionotropic effect, Centhaquin citrate is being tested clinically as a resuscitative agent for the management of hypovolemic shock It acts at the α2B-adrenergic receptor to produce venous constriction followed by an increase in venous return to the heart. These actions are assumed to be capable of resuscitative activity observed by centhaquin citrate, through an increase in cardiac output and tissue perfusion. Pharmacokinetics investigations in animals and humans have shown that centhaquin citrate is well tolerated and has insignificant side effects. Therefore, centhaquin citrate seems to be a promising entity and gaining the interest of researchers to develop it as a resuscitative agent in HS. The review gives insight into the development of centhaquin citrate as a resuscitative agent and provides insight into the associated mechanism of action and molecular signalling to foster future research on CC for its clinical use in HS.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527322666230518115952
Carmen Rubio, Noel Gallardo, Vanessa Mena, Alonso Portilla, Moisés Rubio-Osornio
Background: Bibliometric analysis allows us to quantify and evaluate scientific activity, and it has become increasingly important in all areas of scientific literature. Thanks to these analyses, we can infer where science should put greater efforts into elucidating the underlying mechanisms of diseases that have yet to be fully described or investigated.
Objective: This paper delves into published articles related to the involvement of calcium (Ca2+) channels in epilepsy, which is a condition with a high prevalence in Latin America.
Methods: We followed the scientific publication on SCOPUS and analyzed the impact of publications from Latin America in the field of epilepsy and the study of Ca2+ channels. We identified the countries with the largest number of publications and found that 68% of them were experimental (animal models), while 32% were clinical. We also identified the main journals, growth over time, and citation numbers.
Results: We found a total of 226 works produced by Latin American countries from 1976 to 2022. The countries that have contributed the most to the topic are Brazil, Mexico, and Argentina, with occasional collaborations between them to make contributions to the study of epilepsy and Ca2+ channels. Additionally, we found that the journal with the most citations is Nature Genetics.
Conclusion: The number of authors per article ranges from 1 to 242, and neuroscience journals are the preferred target for researchers, with a predilection for publishing original articles, although 26% of the publications are review articles.
{"title":"The Participation of Ca<sup>2+</sup> Channels in Epilepsy: A Bibliometric Analysis of the Scientific Literature in Latin America.","authors":"Carmen Rubio, Noel Gallardo, Vanessa Mena, Alonso Portilla, Moisés Rubio-Osornio","doi":"10.2174/1871527322666230518115952","DOIUrl":"10.2174/1871527322666230518115952","url":null,"abstract":"<p><strong>Background: </strong>Bibliometric analysis allows us to quantify and evaluate scientific activity, and it has become increasingly important in all areas of scientific literature. Thanks to these analyses, we can infer where science should put greater efforts into elucidating the underlying mechanisms of diseases that have yet to be fully described or investigated.</p><p><strong>Objective: </strong>This paper delves into published articles related to the involvement of calcium (Ca<sup>2+</sup>) channels in epilepsy, which is a condition with a high prevalence in Latin America.</p><p><strong>Methods: </strong>We followed the scientific publication on SCOPUS and analyzed the impact of publications from Latin America in the field of epilepsy and the study of Ca<sup>2+</sup> channels. We identified the countries with the largest number of publications and found that 68% of them were experimental (animal models), while 32% were clinical. We also identified the main journals, growth over time, and citation numbers.</p><p><strong>Results: </strong>We found a total of 226 works produced by Latin American countries from 1976 to 2022. The countries that have contributed the most to the topic are Brazil, Mexico, and Argentina, with occasional collaborations between them to make contributions to the study of epilepsy and Ca<sup>2+</sup> channels. Additionally, we found that the journal with the most citations is Nature Genetics.</p><p><strong>Conclusion: </strong>The number of authors per article ranges from 1 to 242, and neuroscience journals are the preferred target for researchers, with a predilection for publishing original articles, although 26% of the publications are review articles.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871527323666230817145434
Umberto Manera, Enrico Matteoni, Antonio Canosa, Stefano Callegaro, Federico Casale, Daniela Marchis, Rosario Vasta, Cristina Moglia, Adriano Chiò, Andrea Calvo
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder determined by a combination of both genetic and environmental factors. Despite wide investigations, the role of chronic exposure to environmental pollutants is still rather unknown. Among natural toxins, the mycotoxins have received major attention only in the last few years, due to both technical and scientific achievements that allowed to disentangle many important features of the complex fungal biology. Whereas the effects of acute and high-dose mycotoxin exposure are well known, the potential effects of chronic and low-dose exposure on neurodegeneration have not been broadly elucidated. In this review, we have summarized all the studies concerning environmental exposure to unknown substances that caused ALS outbreaks all over the world, reinterpreting in light of the new scientific acquisitions and highlighting the potential and neglected role of mycotoxins. Then, we focused on recent papers about food exposure to mycotoxin, mycobiome and fungal infections in ALS and other neurodegenerative diseases. We analyzed the gaps of current literature that lead to an undervaluation of mycotoxins as detrimental molecules. By listing all the most important mycotoxins and analyzing all the biological pathways that they can affect, we explained the reasons why they need to be considered in the next epidemiological studies on ALS and other neurodegenerative and neuroinflammatory diseases. In conclusion, after suggesting some possible solutions to mitigate mycotoxin exposure risk, we affirm that future collaborations between scientists and policymakers are important to develop sustainable interventions and promote health through dietary diversity.
肌萎缩性脊髓侧索硬化症(ALS)是一种神经退行性疾病,由遗传和环境因素共同决定。尽管进行了广泛的调查,但长期暴露于环境污染物的作用仍然相当未知。在天然毒素中,霉菌毒素直到最近几年才受到人们的广泛关注,这主要归功于技术和科学方面的成就,这些成就使得人们能够揭示复杂的真菌生物学的许多重要特征。虽然急性和高剂量接触霉菌毒素的影响已众所周知,但慢性和低剂量接触霉菌毒素对神经变性的潜在影响尚未得到广泛阐明。在这篇综述中,我们总结了有关环境中暴露于未知物质导致全球爆发 ALS 的所有研究,根据新的科学成果进行了重新解读,并强调了霉菌毒素的潜在作用和被忽视的作用。然后,我们重点讨论了最近有关 ALS 和其他神经退行性疾病中食物接触霉菌毒素、霉菌生物群和真菌感染的论文。我们分析了当前文献中的不足之处,这些不足之处导致霉菌毒素作为有害分子的价值被低估。通过列举所有最重要的霉菌毒素并分析它们可能影响的所有生物通路,我们解释了为什么在下一步对 ALS 及其他神经退行性疾病和神经炎症性疾病的流行病学研究中需要考虑霉菌毒素。最后,我们提出了一些降低霉菌毒素暴露风险的可能解决方案,并申明科学家和政策制定者之间未来的合作对于制定可持续的干预措施和通过饮食多样性促进健康非常重要。
{"title":"Mycotoxins and Amyotrophic Lateral Sclerosis: Food Exposure, Nutritional Implications and Dietary Solutions.","authors":"Umberto Manera, Enrico Matteoni, Antonio Canosa, Stefano Callegaro, Federico Casale, Daniela Marchis, Rosario Vasta, Cristina Moglia, Adriano Chiò, Andrea Calvo","doi":"10.2174/1871527323666230817145434","DOIUrl":"10.2174/1871527323666230817145434","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder determined by a combination of both genetic and environmental factors. Despite wide investigations, the role of chronic exposure to environmental pollutants is still rather unknown. Among natural toxins, the mycotoxins have received major attention only in the last few years, due to both technical and scientific achievements that allowed to disentangle many important features of the complex fungal biology. Whereas the effects of acute and high-dose mycotoxin exposure are well known, the potential effects of chronic and low-dose exposure on neurodegeneration have not been broadly elucidated. In this review, we have summarized all the studies concerning environmental exposure to unknown substances that caused ALS outbreaks all over the world, reinterpreting in light of the new scientific acquisitions and highlighting the potential and neglected role of mycotoxins. Then, we focused on recent papers about food exposure to mycotoxin, mycobiome and fungal infections in ALS and other neurodegenerative diseases. We analyzed the gaps of current literature that lead to an undervaluation of mycotoxins as detrimental molecules. By listing all the most important mycotoxins and analyzing all the biological pathways that they can affect, we explained the reasons why they need to be considered in the next epidemiological studies on ALS and other neurodegenerative and neuroinflammatory diseases. In conclusion, after suggesting some possible solutions to mitigate mycotoxin exposure risk, we affirm that future collaborations between scientists and policymakers are important to develop sustainable interventions and promote health through dietary diversity.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}