CNS & neurological disorders drug targets最新文献

{"title":"Proposed Hypothesis of TWEAK/Fn14 Receptor Modulation in Autism Spectrum Disorder.","authors":"Heena Khan, Vivek Rihal, Amarjot Kaur, Thakur Gurjeet Singh","doi":"10.2174/0118715273330549241015073953","DOIUrl":"10.2174/0118715273330549241015073953","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a complex, multiple etiology that is marked by impaired social interaction, communication, and repetitive behaviour. There is presently no pharmaceutical treatment for the core symptoms of ASD, even though the prevalence of ASD is increasing worldwide. Treatment of autism spectrum disorder involves the interaction of numerous signalling pathways, such as the Wnt/beta-catenin pathway, probiotics and kynurenine pathway, PPAR pathway, PI3K-AKT-mTOR pathway, Hedgehog signaling pathway, etc. The scientific literature has revealed TWEAK/Fn14 to not be explored in the autism spectrum disorder. <i>In vitro</i> and <i>in vivo</i>, TWEAK can control a wide range of cellular responses. Recent research has revealed that TWEAK and Fn14 are expressed in the Central Nervous System (CNS) and upregulated in perivascular endothelial cells, astrocytes, neurons, and microglia in response to various stimuli, including cerebral ischemia. This upregulation is followed by cell death and an increase in Blood-brain Barrier (BBB) permeability. The study has revealed that Aurintricarboxylic Acid (ATA) acts as an agent that suppresses TWEAK/Fn14 signaling. Similarly, from the discussion, it has been emphasized that the proposed molecular TWEAK/Fn14 signalling pathway can be considered as a therapeutic approach in the management of autism spectrum disorder.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"257-262"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549483","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":"Beyond Dopamine: Novel Therapeutic Pathways for Parkinson's Disease Through Receptor Signaling.","authors":"Rashmi Bhushan, Falguni Goel, Shamsher Singh","doi":"10.2174/0118715273325667241212041540","DOIUrl":"10.2174/0118715273325667241212041540","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurological condition characterized by both dopaminergic and non-dopaminergic brain cell loss. Patients with Parkinson's disease have tremors as a result of both motor and non-motor symptoms developing. Idiopathic Parkinson's disease (idiopathic PD) prevalence is increasing in people over 60. The medication L-dopa, which is now on the market, merely relieves symptoms and has several negative effects. In this article, we highlight the therapeutic potential of glucagon-like peptide-1, adenosine A2A, and cannabinoid receptors as attractive targets for enhancing neuroprotection and reducing a variety of motor and non-motor symptoms. Recent research has widened knowledge of new therapeutic targets and detailed cellular mechanisms, providing invaluable insights into the essential roles of cannabinoid receptors, adenosine A2A receptors, and glucagon-like peptide-1 receptors in PD pathogenesis and unique opportunities for drug development for mankind globally.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"434-451"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034038","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":"Epigenetic Threads of Neurodegeneration: TFAM's Intricate Role in Mitochondrial Transcription.","authors":"Aishwarya Bharathi Hemalatha Mallikarjuna Aradya, Prabitha Prabhakaran, Logesh Rajan, Narasimha M Beeraka, Bijo Mathew, Prashantha Kumar Bommenahalli Ravanappa","doi":"10.2174/0118715273334342250108043032","DOIUrl":"10.2174/0118715273334342250108043032","url":null,"abstract":"<p><p>There is a myriad of activities that involve mitochondria that are crucial for maintaining cellular equilibrium and genetic stability. In the pathophysiology of neurodegenerative illnesses, mitochondrial transcription influences mitochondrial equilibrium, which in turn affects their biogenesis and integrity. Among the crucial proteins for keeping the genome in optimal repair is mitochondrial transcription factor A, more commonly termed TFAM. TFAM's non-specific DNA binding activity demonstrates its involvement in the control of mitochondrial DNA (mtDNA) transcription. The role of TFAM in controlling packing, stability, and replication when assessing the quantity of the mitochondrial genome is well recognised. Despite mounting evidence linking lower mtDNA copy numbers to various age-related diseases, the correlation between TFAM abundance and neurodegenerative disease remains insufficient. This review delves into the link between neurodegeneration and mitochondrial dysfunction caused by oxidative stress. Additionally, the article will go into detail about how TFAM controls mitochondrial transcription, which is responsible for encoding key components of the oxidative phosphorylation (OXPHOS) system.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"422-433"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048884","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":"Abnormality of Voltage-Gated Sodium Channels in Disease Development of the Nervous System. A Review Article.","authors":"Bakhtawar Khan, Muhammad Khalid Iqbal, Hamid Khan, Mubin Mustafa Kiyani, Shahid Bashir, Shao Li","doi":"10.2174/0118715273347470250126185122","DOIUrl":"10.2174/0118715273347470250126185122","url":null,"abstract":"<p><p>Sodium channels are necessary for electrical activity in modules of the nervous system. When such channels fail to work properly, it may cause different neurological diseases. This review will discuss how particular mutation in these channels leads to different diseases. Positive alterations can lead to such diseases as epilepsy, or any muscle disorder due to over activation of neurons. Conversely, loss-of-function mutations may cause heart diseases and problems regarding motor and mental activity since neurons are not functioning well because of lost machinery. The review would discuss over familiar channelopathies such as genetic epilepsies, the familial hemiplegic migraine, and Para myotonia congenital and relatively new interrelations with the complex ailments including Alzheimer's, Parkinson's and multiple sclerosis. Thus, knowledge of these mechanisms is important in designing specific therapeutic approaches. There is a rationale for altering the sodium channel activity in the treatment of these neurological disorders by drugs or indeed genetic methods. Thus, the review is undertaken to provide clear distinctions and discuss the issues related to sodium channel mutations for the potential development of individualized medicine. The review also gives information on the function and general distribution of voltage-gated sodium channels (VGSCs), how their activity is controlled, and what their structure is like. The purpose therefore is to draw understanding over the apparently multifaceted functions exerted by VGSCs in the nervous system relative to several diseases. This knowledge is imperative in the attempt to produce treatments for these disabling disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"582-593"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392740","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":"Valproic Acid and Celecoxib Enhance the Effect of Temozolomide on Glioblastoma Cells.","authors":"Oleg Pak, Aleksandra Kosianova, Sergei Zaitsev, Aruna Sharma, Hari Sharma, Igor Bryukhovetskiy","doi":"10.2174/0118715273330268241008220702","DOIUrl":"10.2174/0118715273330268241008220702","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma (GB) is one of the deadliest human brain tumors. The prognosis is unfavorable, chemotherapy with temozolomide (TMZ) may extend the survival period for a patient. The paper aims to evaluate the survival rates among relapsing GB patients, who have been treated with valproic acid (VPA), and to study its effect on tumor cells when combined with TMZ and celecoxib (CXB).</p><p><strong>Materials and methods: </strong>The research is based on retrospective analysis of the data from GB patients who had been treated with VPA as a part of a complex treatment protocol and reoperated due to a GB relapse. The experimental study involved cancer cells of C6, U87, and T98G lines. GB was modeled on Wistar rats. The research was approved by the ethics committee. Differences in groups were considered significant at p < 0.05 Results: The median of overall survival among GB patients who took VPA was 22 months, and for those who did not take VPA - 13 months. The <i>in vitro</i> experiment showed the half-maximal inhibitory concentration (IC₅₀) of TMZ for various lines of cancer cells (CCs) varying from 435.3 to 844 μM. IC₅₀ VPA for CCs of U87MG, T98G, and С6 lines was 1510, 3900, and 3600 μM: IC₅₀ CXB for those lines of CCs was 30.1 μM, 41.07, and 48.4 μM respectively. VPA significantly enhanced the anti-glioma effect of TMZ on the U87 line of CCs, while CCs of C6 and T98G lines proved to be most susceptible to the combination of CXB and TMZ. The combination of VPA with CXB increased the anti-glioma effect of TMZ both <i>in vitro</i> and <i>in vivo</i>, also reducing the tumor size (р < 0.05) and prolonging the survival period among experimental animals.</p><p><strong>Conclusion: </strong>VPA and CXB enhance the effect of TMZ on glioblastoma cells.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"375-381"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483134","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":"The Gut Microbiota-Brain Axis: A New Frontier in Alzheimer's Disease Pathology.","authors":"Meenakshi Dhanawat, Garima Malik, Kashish Wilson, Sumeet Gupta, Nidhi Gupta, Satish Sardana","doi":"10.2174/0118715273302508240613114103","DOIUrl":"10.2174/0118715273302508240613114103","url":null,"abstract":"<p><p>Dr. Aloysius Alzheimer, a German neuropathologist and psychiatrist, recognized the primary instance of Alzheimer's disease (AD) for a millennium, and this ailment, along with its related dementias, remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia, with Alzheimer's illness contributing to between 60 and 70% of the instances, estimated through the World Health Organization. In addition, 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore, age, environmental circumstances, and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease, which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of Nmethyl D-aspartate). In 2020, the FDA provided approval on anti-amyloid drugs. According to mounting scientific data, this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the \"two-way\" microbiota-gut-brain axis. Along this axis, the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota, for instance, can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review, the effects of the microbiota- gut-brain axis on AD pathogenesis will be discussed.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"7-20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536172","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":"Foreign Contaminants Target Brain Health.","authors":"Uma Agarwal, Arzoo Pannu, Rajiv Kumar Tonk","doi":"10.2174/0118715273338071241213101016","DOIUrl":"10.2174/0118715273338071241213101016","url":null,"abstract":"<p><p>Neurodisease, caused by undesired substances, can lead to mental health conditions like depression, anxiety and neurocognitive problems like dementia. These substances can be referred to as contaminants that can cause damage, corruption, and infection or reduce brain functionality. Contaminants, whether conceptual or physical, have the ability to disrupt many processes. These observations motivate us to investigate contaminants and neurotoxicity collaboratively. This study investigates the link between pollutants and neuro-disease, examining transmission pathways and categorization. It also provides information on resources, causes, and challenges to minimize contamination risks. Contamination may cause various neuro-diseases, including Alzheimer's, Parkinson's, multi-system atrophy, Huntington's, autism spectrum disorder, psychiatric disorder, dementia, meningitis, encephalitis, schizophrenia, anxiety, and depression. The negative effects depend on the nature and extent of exposure. A comprehensive literature search was conducted using databases such as PubMed and Scopus, focusing on studies published till 2024. Studies were selected based on their examination of the relationship between environmental contaminants and brain health, emphasizing transmission pathways and the resulting neurological outcomes. Findings indicate that contaminants can penetrate the blood-brain barrier (BBB) via nasal, gut, and auditory routes, triggering harmful neurophysiological processes. This review highlights the urgent need for increased global awareness, policy interventions, and preventive measures to mitigate the long-term impacts of environmental contaminants on brain health, particularly in emerging nations.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"353-374"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium Chloride Rescues Dopaminergic Neurons in a Parkinson's Disease Rat Model Challenged with Rotenone.","authors":"Eman Allam, Sary Khalil Abdel-Ghafar, Manal Hussein, Ahmed Al-Emam, Khaled Radad","doi":"10.2174/0118715273365449250224090655","DOIUrl":"10.2174/0118715273365449250224090655","url":null,"abstract":"<p><strong>Introduction/background: </strong>Parkinson's disease, the second most common neurodegenerative disease, is still lacking an effective treatment that can stop dopaminergic cell loss in substantia nigra and alter disease progression. The present study aimed to investigate the neuroprotective efficacy of lithium chloride in a rotenone-induced rat model of Parkinson's disease.</p><p><strong>Methods: </strong>Forty male Sprague Dawley rats were assigned into 4 groups: control, rotenone-, rotenone and lithium chloride- and lithium chloride-treated groups. Rotenone (2 mg/kg b.w.) and lithium chloride (60 mg/kg b.w.) were, respectively, administered subcutaneously and orally five times a week for 5 weeks. At the end of each treatment, the neuroprotective efficacy of lithium chloride against rotenone-induced derangements was evaluated by some behavioral tests, biochemical analysis, gel electrophoresis, histopathology, and immunohistochemistry.</p><p><strong>Results: </strong>Rotenone significantly resulted in neurobehavioral deficits, gastrointestinal dysfunction, decreased activities of catalase and superoxide dismutase, depleted glutathione, and increased levels of malondialdehyde. It also caused DNA fragmentation and loss of dopaminergic neurons in substantia nigra and decreased striatal tyrosine hydroxylase staining intensity. Concomitant treatment of rats with rotenone and lithium chloride significantly improved behavioral impairment and markedly alleviated gastrointestinal dysfunction. It also increased catalase activity and decreased malondialdehyde levels, indicating antioxidant effects. Moreover, it decreased DNA fragmentation, rescued dopaminergic neurons, and increased tyrosine hydroxylase immunoreactivity in the striatum compared to the rotenone-treated group.</p><p><strong>Conclusion: </strong>Lithium chloride rescued dopaminergic neurons in a rotenone model of PD, possibly through the improvement of behavioral deficits, decreasing oxidative stress, and reducing DNA damage.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"636-647"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Predisposition and Severity of Eating Disorders- A Review.","authors":"Md Harun Rashid, Neha Deora, Shashidhar Ravindra Kolur, Suttur S Malini, Priyankar Sen","doi":"10.2174/0118715273372810250214054917","DOIUrl":"10.2174/0118715273372810250214054917","url":null,"abstract":"<p><p>Eating disorders (EDs) are multifaceted psychiatric conditions with significant genetic, psychological, and environmental components. This review provides a comprehensive analysis of the genetic underpinnings and key molecular pathways contributing to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Genetic studies, particularly genome-wide association studies (GWAS), have identified key loci associated with ED susceptibility, with heritability estimates for these disorders ranging between 48% and 74%. Among the critical genes explored, the Agouti-related protein (AGRP), ghrelin (GHRL), and brain-derived neurotrophic factor (BDNF) pathways emerge as pivotal regulators of appetite control, energy balance, and reward systems, offering insights into ED etiology. These pathways are modulated by environmental factors and often dysregulated in individuals with EDs, linking abnormal eating behaviors to disturbances in neurobiological functions. EDs also show a strong association with comorbid psychiatric disorders, such as depression and anxiety, and pose significant physical health risks, including cardiovascular disease and metabolic disturbances. Exploring the intricate genetic and neurobiological mechanisms underlying eating disorders (EDs) paves the way for more effective prevention, early detection, and tailored treatment strategies. This review highlights the potential of utilizing genetic insights to enhance diagnostic and intervention strategies, ultimately leading to better outcomes for individuals impacted by eating disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"498-510"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484731","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":"Neurotrophins in Peripheral Neuropathy: Exploring Pathophysiological Mechanisms and Emerging Therapeutic Opportunities.","authors":"Suman Samaddar, Moqbel Ali Moqbel Redhwan, Mohan Muttanahally Eraiah, Raju Koneri","doi":"10.2174/0118715273327121240820074049","DOIUrl":"10.2174/0118715273327121240820074049","url":null,"abstract":"<p><p>Neuropathies, which encompass a wide array of peripheral nervous system disorders, present significant challenges due to their varied causes, such as metabolic diseases, toxic exposures, and genetic mutations. This review article, focused on the critical role of neurotrophins in peripheral neuropathy, highlights the intricate balance of neurotrophins necessary for nerve health and the pathophysiological consequences when this balance is disturbed. Neurotrophins, including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT- 3), and Neurotrophin-4 (NT-4), are essential for neuronal survival, axonal growth, and synaptic plasticity. Their signaling pathways are crucial for maintaining peripheral nervous system integrity, primarily <i>via</i> the Tropomyosin receptor kinase (Trk) receptors and the p75 neurotrophin receptor p75(NTR). Dysregulation of neurotrophins is implicated in various neuropathies, such as diabetic neuropathy and chemotherapy-induced peripheral neuropathy, leading to impaired nerve function and regeneration. Understanding neurotrophin signaling intricacies and their alterations in neuropathic conditions is crucial for identifying novel therapeutic targets. Recent advancements illuminate neurotrophins' potential as therapeutic agents, promising disease-modifying treatments by promoting neuronal survival, enhancing axonal regeneration, and improving functional recovery post-nerve injury. However, translating these molecular insights into effective clinical applications faces challenges, including delivery methods, target specificity, and the instability of protein- based therapies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"91-101"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141992","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}