CNS & neurological disorders drug targets最新文献

{"title":"Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors.","authors":"Neha Rana, Parul Grover","doi":"10.2174/0118715273340983241018095529","DOIUrl":"https://doi.org/10.2174/0118715273340983241018095529","url":null,"abstract":"<p><p>Parkinson's disease is a neurodegenerative condition characterized by slow movement (bradykinesia), tremors, and muscle stiffness. These symptoms occur due to the degeneration of dopamine- producing neurons in the substantia nigra region of the brain, leading to reduced dopamine levels. The development of Parkinson's Disease (PD) involves a combination of genetic and environmental factors. PD is associated with abnormal regulation of the monoamine oxidase (MAO) enzyme. Monoamine oxidase inhibitors (MAOIs) are an important class of drugs used to treat PD and other neurological disorders. In the early stages of PD, monotherapy with MAO-B inhibitors has been shown to be both safe and effective. These inhibitors are also commonly used as adjuncts in long-term disease management, as they can improve both motor and non-motor symptoms, reduce \"OFF\" periods, and potentially slow disease progression. However, current MAO-B inhibitors come with side effects like dizziness, nausea, vomiting, light-headedness, and fainting. Therefore, accelerating the development of new MAO-B inhibitors with fewer side effects is crucial. This review explores natural compounds that may inhibit monoamine oxidase B (MAO-B), focusing on key findings from the past seven years. It highlights the most effective heterocyclic compounds against MAO-B, including thiazolyl hydrazone, pyridoxine-resveratrol, pyridazine, isoxazole, oxadiazole, benzothiazole, benzoxazole, coumarin, caffeine, pyrazoline, piperazine, piperidine, pyrrolidine, and morpholine derivatives. The review covers in vitro, in silico, and in vivo data, along with the structure- activity relationship of these compounds. These findings offer valuable insights for the development of more effective MAO-B inhibitors and advancements in Parkinson's disease research.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585260","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":"Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-Loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways.","authors":"Nitish Kumar, Nidhi Tyagi, Sidharth Mehan, Alok Pratap Singh","doi":"10.2174/0118715273336107241015100912","DOIUrl":"https://doi.org/10.2174/0118715273336107241015100912","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a persistent autoimmune condition characterized by inflammation and neurodegeneration. The current efficacy of treatments is limited, which has generated interest in developing neuroprotective strategies. Solid lipid nanoparticles (SLNs) and probiotics are potential drug delivery vehicles for targeting the CNS (Central nervous system), regulating immune responses, and supporting neuroprotection in neurological conditions.</p><p><strong>Methods: </strong>The study investigates how SLNs containing RSG (rosiglitazone) and probiotics can protect the nervous system in cases of MS. We administered toxin EtBr (Ethidium bromide) from day 1 to day 7, later followed by the treatment from day 8 to day 35. During this time interval, various behavioural parameters have been performed. Further, after 35th day, blood plasma of animals was collected to study complete CBC profiling and animals were sacrificed. Then, biochemical and molecular studies, gross morphology of brain sectioning, histopathological evaluation and estimation of fatty acid content in fecal matter were performed.</p><p><strong>Results: </strong>RSG shows neuroprotective effects by blocking the STAT-3 and mTOR signaling pathways and increasing the production of PPAR-gamma. GW9662, a PPAR-gamma antagonist given at a dose of 2 mg/kg (i.p), was utilized to evaluate the role of PPAR-gamma and to compare the efficacy of RSG and probiotic-loaded SLNs in potentially providing neuroprotection. The relationship between RSG and the STAT-3, mTOR, and PPAR-gamma pathways in MS was confirmed and validated using in-silico analysis. RSG and probiotic-loaded SLNs modulate the complete blood profiling of rats and improve the symptoms of MS. We assessed the diagnostic capabilities of different biological samples such as cerebrospinal fluid, blood plasma, and brain homogenates (specifically from the hippocampus, striatum, cortex, and midbrain) to analyze neurochemical changes linked to neurobehavioral changes in the progression of MS.</p><p><strong>Conclusion: </strong>The study showed that combining RSG and probiotics in an experimental medication form improved symptoms of MS more effectively than using RSG alone. This improvement is likely due to changes in STAT-3, mTOR, and PPAR-gamma signaling pathways.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570703","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":null,"pages":null},"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":"Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease.","authors":"Parneet Kaur, Heena Khan, Amarjot Kaur Grewal, Kamal Dua, Sachin Kumar Singh, Gaurav Gupta, Thakur Gurjeet Singh","doi":"10.2174/0118715273321002240919102841","DOIUrl":"https://doi.org/10.2174/0118715273321002240919102841","url":null,"abstract":"<p><p>Alzheimer's disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world's population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549481","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":"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":"https://doi.org/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. In vitro and in vivo, 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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","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":"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":null,"pages":null},"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":"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","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":"Hypoxia-inducible Factor-1α Pathway in Cerebral Ischemia: From Molecular Mechanisms to Therapeutic Targets.","authors":"Veerta Sharma, Thakur Gurjeet Singh","doi":"10.2174/0118715273324551241008111827","DOIUrl":"https://doi.org/10.2174/0118715273324551241008111827","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic injury to the brain can result in a variety of life-threatening conditions, mortality, or varying degrees of disability. Hypoxia-inducible factor 1α (HIF 1α), an oxygen- sensitive transcription factor that controls the adaptive metabolic response to hypoxia, is a critical constituent of cerebral ischemia. It participates in numerous processes, such as metabolism, proliferation, and angiogenesis, and plays a major role in cerebral ischemia.</p><p><strong>Methods: </strong>Through the use of a number of different search engines like Scopus, PubMed, Bentham, and Elsevier databases, a literature review was carried out for investigating the pharmacological modulation of HIF-1α pathways for the treatment of cerebral ischemia.</p><p><strong>Results: </strong>Various signalling pathways, such as Mitogen-activated protein kinase (MAPK), Janus kinase/ signal transducers and activators (JAK/STAT), Phosphoinositide-3-kinase (PI3-K), and cAMPresponse element binding protein (CREB) play a vital role in modulation of HIF-1α pathway, which helps in preventing the pathogenesis of cerebral ischemia.</p><p><strong>Conclusion: </strong>The pharmacological modulation of the HIF-1α pathway via various molecular signalling pathways, such as PI3-K, MAPK, CREB, and JAK/STAT activators, offer a promising prospect for future interventions and treatment for cerebral ischemia.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483132","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, Alexandra Kosianova, Sergei Zaitsev, Aruna Sharma, Hari Sharma, Igor Bryukhovetskiy","doi":"10.2174/0118715273330268241008220702","DOIUrl":"https://doi.org/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 in vitro 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 in vitro and in vivo, 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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","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":"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":null,"pages":null},"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}