CNS & neurological disorders drug targets最新文献

{"title":"Amyotrophic Lateral Sclerosis (ALS): An Overview of Genetic and Metabolic Signaling Mechanisms.","authors":"Jose Augusto Nogueira-Machado, Franscisco das Chagas Lima E Silva, Fabiana Rocha-Silva, Nathalia Gomes","doi":"10.2174/0118715273315891240801065231","DOIUrl":"10.2174/0118715273315891240801065231","url":null,"abstract":"<p><p>Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive, and incurable disease. Sporadic (sALS) accounts for ninety percent of ALS cases, while familial ALS (fALS) accounts for around ten percent. Reports have identified over 30 different forms of familial ALS. Multiple types of fALS exhibit comparable symptoms with mutations in different genes and possibly with different predominant metabolic signals. Clinical diagnosis takes into account patient history but not genetic mutations, misfolded proteins, or metabolic signaling. As research on genetics and metabolic pathways advances, it is expected that the intricate complexity of ALS will compound further. Clinicians discuss whether a gene's presence is a cause of the disease or just an association or consequence. They believe that a mutant gene alone is insufficient to diagnose ALS. ALS, often perceived as a single disease, appears to be a complex collection of diseases with similar symptoms. This review highlights gene mutations, metabolic pathways, and muscle-neuron interactions.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"83-90"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019849","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":"Modeling of Parkinson's Disease in Different Models.","authors":"Iqra Subhan, Yasir Hasan Siddique","doi":"10.2174/0118715273326866240922193029","DOIUrl":"10.2174/0118715273326866240922193029","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a progressive disorder worldwide and its etiology remains unidentified. Over the last few decades, animal models of PD have been extensively utilized to explore the development and mechanisms of this neurodegenerative condition. Toxic and transgenic animal models for PD possess unique characteristics and constraints, necessitating careful consideration when selecting the appropriate model for research purposes. Animal models have played a significant role in uncovering the causes and development of PD, including its cellular and molecular processes. These models suggest that the disorder arises from intricate interplays between genetic predispositions and environmental influences. Every model possesses its unique set of strengths and weaknesses. This review provides a critical examination of animal models for PD and compares them with the features observed in the human manifestation of the disease.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"102-114"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362565","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":"Vitamin D and Neurological Health: Unraveling Risk Factors, Disease Progression, and Treatment Potential.","authors":"Abdullah Al Noman, Halima Afrosa, Imanul Kabir Lihu, Onusree Sarkar, Naimur Rahman Nabin, Monty Datta, Rashmi Pathak, Himanshu Sharma","doi":"10.2174/0118715273330972241009092828","DOIUrl":"10.2174/0118715273330972241009092828","url":null,"abstract":"<p><p>This study explores the complex link between vitamin D and neurological illnesses, focusing on how vitamin D affects possible risk factors, therapeutic applications, and the trajectory of the disease. An epidemiological study has linked vitamin D insufficiency to several neurological conditions, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. It is hypothesized that immunomodulatory and anti-inflammatory properties of vitamin D contribute to its neuroprotective effects. Two major mechanisms in dementia include neuroinflammation and oxidative stress. Adequate levels of vitamin D have been shown in both animal models and human studies to enhance both clinical outcomes and the duration of illness in those who have it. Other ways that vitamin D contributes to its therapeutic potential include the production of neurotrophic factors, control over neurotransmitter synthesis, and preservation of the blood-brain barrier. Despite the encouraging outcomes, research is still being conducted to determine the optimal dosage and long-term benefits of vitamin D supplementation on brain function. In order to furnish precise directives and clarify the processes behind the neuroprotective impacts of vitamin D, future research must focus on large-scale randomized controlled studies. . This study highlights the significance of maintaining adequate levels of vitamin D as a modifiable risk factor for neurological disorders. Further study is also required to comprehend the possible medical benefits of this vitamin fully.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"245-256"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514738","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":"Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment.","authors":"Umer Anayyat, Faiza Ahad, Bushra Muhammad Fordil, Hajra Hameed, Mengqing Li, Qinyao Yu, Yunpeng Wei, Xiaomei Wang","doi":"10.2174/0118715273318429240812094557","DOIUrl":"10.2174/0118715273318429240812094557","url":null,"abstract":"<p><p>In this review, we have discussed the invasive and non-invasive treatment options for Parkinson's Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"165-180"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121571","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":"Recent Trends in Physical Therapy Interventions and Neuromodulation Techniques to Improve Neurorehabilitation.","authors":"Patralika Nath, Barnana Roy, Soumya Saswati Panigrahi, Kamirul Islam, Asim Kumar Basak","doi":"10.2174/0118715273341882250114054733","DOIUrl":"10.2174/0118715273341882250114054733","url":null,"abstract":"<p><p>Promoting neuroplasticity for better recovery and function restoration has lately become the focus of rehabilitation techniques for individuals with neurologic disorders. A rapidly expanding medical specialty, neuromodulation includes a broad variety of methods for activating particular neurological pathways, such as Transcranial magnetic stimulation (TMS), Transcranial direct current stimulation (tDCS), peripheral nerve stimulation, and SCS, among many others. Research on the use of neuromodulation in the context of spinal cord injury (SCI) is limited, in contrast to the abundance of literature on its potential benefits in chronic pain treatment. Combining exercise with non-invasive neuromodulation improves recovery outcomes for some patient groups, according to our research. While we mostly focus on the motor components of recovery, we do briefly mention the non-motor effects of these disorders. The difficulties of applying ideas in clinical practice and the gaps in the existing research are also brought to light. In order to better customize the individual neuroplastic responses associated with each disease, we identify research gaps and propose routes for future investigations. This review is useful for rehabilitation professionals and researchers since it focuses on neuroplastic exercise treatments for specific illnesses and diagnoses. Few studies have used long-term randomized-controlled trials, even though these approaches have great promise for enhancing overall functionality and impairment levels. If these novel modalities may be therapeutically employed to reduce pain, restore function, and improve the quality of life for individuals impacted, then more study is required to support them.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"521-545"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416321","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":"Barbigerone against Lipopolysaccharide-Induced Memory Deficit in Rats via Alteration of Inflammatory and Oxidative Stress Pathway: <i>In vivo</i>, Molecular Docking and Molecular Dynamics Simulations Study.","authors":"Muhammad Shahid Nadeem, Jalaluddin Azam Khan, Fahad A Al-Abbasi, May M Alqurashi, Azizah Salim Bawadood, Sami I Alzarea, Nadeem Sayyed, Gaurav Gupta, Imran Kazmi","doi":"10.2174/0118715273332347250122112850","DOIUrl":"10.2174/0118715273332347250122112850","url":null,"abstract":"<p><strong>Introduction: </strong>Memory loss and cognitive decline are prominent symptoms of various neurodegenerative diseases, impacting daily activities and posing a significant burden on healthcare systems. The study aimed to explore the effect of barbigerone against LPS-induced memory impairment in rats and may offer novel therapeutics for neurodegenerative diseases.</p><p><strong>Methods: </strong>A total of 30 male Wistar rats were utilized and subsequently divided into five distinct experimental groups: group I received saline as a control, group II- received LPS, group III - received LPS, and barbigerone (10 mg/kg/p.o.), group IV- received LPS and a higher dose of barbigerone (20 mg/kg/p.o.), and group V -barbigerone alone (20 mg/kg/p.o.). Behavioural test was performed through the Morris water maze (MWM) and Y-maze test. Biochemical markers such as oxidative, proinflammatory, apoptotic, and further molecular docking and simulations elucidate the mechanisms of barbigerone effects.</p><p><strong>Results: </strong>Barbigerone significantly improved the learning capacity of rats in both the MWM and Y-maze tests, indicating enhanced memory and reduced latency times. Furthermore, barbigerone exhibited beneficial effects on oxidative stress and inflammation markers, suggesting its potential to protect against neuronal damage and promote cognitive function. Based on molecular docking, barbigerone showed a greater binding affinity with different intermolecular interactions; among them, NF-KB (ISVC) had the most potent interaction. Molecular dynamics simulations were performed to assess the stability and convergence of complexes formed by Barbigerone with 1NME_ Barbigerone, 1SVC_Barbigerone, and 4AQ3 4AQ3_Barbigerone.</p><p><strong>Conclusion: </strong>These findings demonstrate that barbigerone possesses neuronal protective effects against LPS-induced memory deficits in rats by restoring endogenous antioxidant and pro-inflammatory cytokines.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"554-576"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392743","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":"Internet of Medical Things (IoMT) for Alzheimer Patient's Outcome.","authors":"Thangavel Lakshmipriya, Subash C B Gopinath","doi":"10.2174/0118715273371149250218081425","DOIUrl":"10.2174/0118715273371149250218081425","url":null,"abstract":"<p><p>The Internet of Medical Things (IoMT) is a network system that connects devices with medical and healthcare for the ultimate aim of collecting, transmitting, and analyzing the acquired data in the presence of the internet. A wide range of equipment and monitoring systems have been generated with IoMT, and they permit real-time monitoring, sharing the data, analysis, patient care, and for efficient operation. At the advanced level, it is highly facilitated with remote patient digital monitoring and telemedicine. IoMT has a significant potential to enhance the care of Alzheimer's disease patients to overcome issues with a progressive neurological condition, memory loss, cognition, and behavior. This study aims to bring the potential of the Internet of Things (IoT) to be implemented in the Internet of Medical Things (IoMT), with a special focus on Alzheimer's disease patients.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"491-493"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484732","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":"Parkinson's Disease: A Progressive Neurodegenerative Disorder and Structure-Activity Relationship of MAO Inhibitor Scaffolds as an Important Therapeutic Regimen.","authors":"Salauddin, Syed Amir Azam Zaidi, Mohammed Ubaid, Saniya Shamim, Mohd Javed Naim, Suruchi Khanna, Ozair Alam","doi":"10.2174/0118715273324300241010054029","DOIUrl":"https://doi.org/10.2174/0118715273324300241010054029","url":null,"abstract":"<p><p>Parkinson's disease is considered an advancing neurodegenerative disorder with unknown causes, and its association with some risk factors, including aging, family history, and exposure to chemicals, makes it the second most common occurring neurodegenerative disorder throughout the world with increasing prevalence. Parkinson's disease is associated with slow movement, rigidity, tremors, imbalance, depression, anxiety, cognitive impairment, orthostasis, hyperhidrosis, sleep disorders, pain, and sensory disturbances. In recent decades, there has been a rise in research on the development of effective and potential therapies for the treatment of Parkinson's disease. An important target for neuroprotection is Monoamine Oxidases (MAO), which hydrolyze neurotransmitters like dopamine and produce very reactive free radicals as a by-product. Aging and neurodegenerative illnesses cause overexpression in the brain, which exacerbates neuronal loss. The treatment of Parkinson's disease with MAO inhibitors has shown promising outcomes. Herein, we reported characteristic features of Parkinson's disease, various treatment strategies, and the SAR of potential drugs that can be explored further as lead for the development of newer molecules with improved pharmacological profiles.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559739","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":"In Silico and ADMET Studies of Spiro-Quinazoline Compounds as Acetylcholine Esterase Inhibitors Against Alzheimer's Disease.","authors":"Abdulelah Aljuaid, Osama Abdulaziz, Mamdouh Allahyani, Mazen Almehmadi, Abdullah Yahya Abdullah Alzahrani, Shivani Verma, Mohd Yusuf, Mohammad Asif","doi":"10.2174/0118715273315412241009092249","DOIUrl":"https://doi.org/10.2174/0118715273315412241009092249","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors are used in primary pharmacotherapy for numerous neurodegenerative conditions, providing their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, quinazoline derivatives have emerged as a compelling model for neurodegenerative disease treatment, showcasing promising pharmacological features. Their unique structural features and pharmacokinetic profiles have sparked interest in their potential efficacy and safety across diverse neurodegenerative disorders. The exposure of quinazoline derivatives as a potential therapeutic way underscores the imperative for continued research exploration. Their multifaceted mechanisms of action and ability to target various pathways implicated in neurodegeneration offer exciting prospects for developing novel, effective, and well-tolerated treatments. Further investigations into their pharmacological activities and precise therapeutic roles are essential to advance our understanding of neurodegenerative disease pathophysiology and promote the development of modern therapeutic strategies to address this critical medical challenge.</p><p><strong>Methods: </strong>Quinazoline derivatives have gained eminent acetylcholinesterase (AChE) inhibitory activity. Their ability to effectively modulate AChE activity makes them promising candidates for treating neurological disorders, particularly Alzheimer's disease (AD). Their intricate molecular structures confer selectivity and affinity for AChE, offering potential for the development of novel therapeutic agents targeting cholinergic pathways. Hence, in this study, we designed, synthesized, and characterized a series of spiro[cycloalakane-1,2'-quinazoline derivatives (1-6) to assess their possible AChE inhibiting ability using docking into the active sites.</p><p><strong>Results: </strong>The AChE inhibitory potential of spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) was explored via docking studies of the AChE active site. The findings revealed significant inhibitory activity and highlighted the promising nature of these derivatives.</p><p><strong>Conclusion: </strong>The synthesized spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) exhibited their notable potential as AChE inhibitors. The observed significant inhibitory activity suggested that these derivatives warrant further exploration as candidates for developing therapeutic agents in AChE inhibitory pathways. This study emphasizes the relevance of quinazoline derivatives in searching for novel treatments for neurological disorders, particularly associated with cholinergic dysfunction, and they could be a useful alternative therapeutic agent.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549482","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":"An Insight into Medicinal Chemistry and SAR Studies of Cholinesterase and BACE-1 Inhibitors for Alzheimer's Disease.","authors":"Abhimannu Shome, Keshav Taruneshwar Jha, Chahat, Viney Chawla, Pooja A Chawla","doi":"10.2174/0118715273315191241002115155","DOIUrl":"https://doi.org/10.2174/0118715273315191241002115155","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a serious neurodegenerative condition that predominantly impacts the cholinergic neurons of the entorhinal cortex and hippocampal regions, playing a critical role in learning, navigation, and brain processing. This paper aims to discuss the three main hypotheses of Alzheimer's disease, focusing on neurotoxicity and neurodegeneration caused by mitochondrial dysfunction and ROS production, particularly analyzing the susceptibility differences between genders. Our comprehensive review focuses on significant findings from the past five years, particularly on Cholinesterase (ChE) and BACE-1 inhibitors. Researchers have conducted a detailed analysis of in vitro, in silico, and in vivo data, incorporating extensive Structure-Activity Relationship (SAR) studies. The reviewed papers have been sourced from platforms, such as Google Scholar, Semantic Scholar, and ClinicalTrials.gov, and have been selected based on their AChE and BACE-1 inhibitory activity and structural motif similarity. The review identifies the most effective compounds targeting ChE and BACE-1, highlighting acridine, dihydropyridine, and thiazole-coumarin hybrids for ChE inhibition, and oxadiazole, benzofuran, and dihydropyrimidinone for BACE-1 inhibition. This demonstrates a diverse array of potent heterocyclic hybrids. The review presents a varied compilation of scaffolds showing promise in treating Alzheimer's disease, highlighting the potential of specific compounds against ChE and BACE-1. Given the critical insights derived from our analysis, we posit that this compilation will substantially contribute to the ongoing efforts to combat neurodegeneration and prolong dementia, underscoring the importance of continuous research in this domain.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483130","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}