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1.
Bol. latinoam. Caribe plantas med. aromát ; 23(3): 349-370, mayo 2024. ilus
Artigo em Inglês | LILACS | ID: biblio-1538077

RESUMO

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.


Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.


Assuntos
Extratos Vegetais/uso terapêutico , Vitis/química , Doenças do Sistema Nervoso/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico
2.
Prog Mol Biol Transl Sci ; 205: 23-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38789181

RESUMO

Recent evolution in drug repurposing has brought new anticipation, especially in the conflict against neurodegenerative diseases (NDDs). The traditional approach to developing novel drugs for these complex disorders is laborious, time-consuming, and often abortive. However, drug reprofiling which is the implementation of illuminating novel therapeutic applications of existing approved drugs, has shown potential as a promising strategy to accelerate the hunt for therapeutics. The advancement of computational approaches and artificial intelligence has expedited drug repurposing. These progressive technologies have enabled scientists to analyse extensive datasets and predict potential drug-disease interactions. By prospecting into the existing pharmacological knowledge, scientists can recognise potential therapeutic candidates for reprofiling, saving precious time and resources. Preclinical models have also played a pivotal role in this field, confirming the effectiveness and mechanisms of action of repurposed drugs. Several studies have occurred in recent years, including the discovery of available drugs that demonstrate significant protective effects in NDDs, relieve debilitating symptoms, or slow down the progression of the disease. These findings highlight the potential of repurposed drugs to change the landscape of NDD treatment. Here, we present an overview of recent developments and major advances in drug repurposing intending to provide an in-depth analysis of traditional drug discovery and the strategies, approaches and technologies that have contributed to drug repositioning. In addition, this chapter attempts to highlight successful case studies of drug repositioning in various therapeutic areas related to NDDs and explore the clinical trials, challenges and limitations faced by researchers in the field. Finally, the importance of drug repositioning in drug discovery and development and its potential to address discontented medical needs is also highlighted.


Assuntos
Reposicionamento de Medicamentos , Humanos , Animais , Doenças do Sistema Nervoso/tratamento farmacológico , Descoberta de Drogas
3.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731911

RESUMO

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.


Assuntos
Fator de Crescimento do Tecido Conjuntivo , Descoberta de Drogas , Humanos , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Descoberta de Drogas/métodos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Fibrose , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
4.
Comput Biol Med ; 175: 108536, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701592

RESUMO

In response to the shortcomings in data quality and coverage for neurological and psychiatric disorders (NPDs) in existing comprehensive databases, this paper introduces the DTNPD database, specifically designed for NPDs. DTNPD contains detailed information on 30 NPDs types, 1847 drugs, 514 drug targets, 64 drug combinations, and 61 potential target combinations, forming a network with 2389 drug-target associations. The database is user-friendly, offering open access and downloadable data, which is crucial for network pharmacology studies. The key strength of DTNPD lies in its robust networks of drug and target combinations, as well as drug-target networks, facilitating research and development in the field of NPDs. The development of the DTNPD database marks a significant milestone in understanding and treating NPDs. For accessing the DTNPD database, the primary URL is http://dtnpd.cnsdrug.com, complemented by a mirror site available at http://dtnpd.lyhbio.com.


Assuntos
Transtornos Mentais , Doenças do Sistema Nervoso , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Bases de Dados de Produtos Farmacêuticos , Bases de Dados Factuais
5.
Neurochem Int ; 177: 105771, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761853

RESUMO

For most diseases and disorders occurring in the brain, the full causes behind them are yet unknown, but many show signs of dysfunction of amino acid transporters or abnormalities in amino acid metabolism. The blood-brain barrier (BBB) plays a key role in supporting the function of the central nervous system (CNS). Because of its unique structure, the BBB can maintain the optimal environment for CNS by controlling the passage of hydrophilic molecules from blood to the brain. Nutrients, such as amino acids, can cross the BBB via specific transporters. Many amino acids are essential for CNS function, and dysfunction of these amino acid transporters can lead to abnormalities in amino acid levels. This has been linked to causes behind certain genetic brain diseases, such as schizophrenia, autism spectrum disorder, and Huntington's disease (HD). One example of crucial amino acids is L-Cys, the rate-limiting factor in the biosynthesis of an important antioxidant, glutathione (GSH). Deficiency of L-Cys and GSH has been linked to oxidative stress and has been shown as a plausible cause behind certain CNS diseases, like schizophrenia and HD. This review presents the current status of potential L-Cys therapies and gives future directions that can be taken to improve amino acid transportation related to distinct CNS diseases.


Assuntos
Sistemas de Transporte de Aminoácidos , Cisteína , Doenças do Sistema Nervoso , Fármacos Neuroprotetores , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Animais , Cisteína/metabolismo , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Sistemas de Transporte de Aminoácidos/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos
6.
Neurochem Res ; 49(7): 1838-1850, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38727984

RESUMO

Menaquinone-4 (MK-4) is an isoform of vitamin K2 that has been shown to exert various biological actions besides its functions in blood coagulation and bone metabolism. Here we examined the effect of MK-4 on a mouse model of intracerebral hemorrhage (ICH). Daily oral administration of 200 mg/kg MK-4 starting from 3 h after induction of ICH by intrastriatal collagenase injection significantly ameliorated neurological deficits. Unexpectedly, MK-4 produced no significant effects on various histopathological parameters, including the decrease of remaining neurons and the increase of infiltrating neutrophils within the hematoma, the increased accumulation of activated microglia/macrophages and astrocytes around the hematoma, as well as the injury volume and brain swelling by hematoma formation. In addition, ICH-induced increases in nitrosative/oxidative stress reflected by changes in the immunoreactivities against nitrotyrosine and heme oxygenase-1 as well as the contents of malondialdehyde and glutathione were not significantly affected by MK-4. In contrast, MK-4 alleviated axon tract injury in the internal capsule as revealed by neurofilament-H immunofluorescence. Enhanced preservation of the corticospinal tract by MK-4 was also confirmed by retrograde labeling of neurons in the primary motor cortex innervating the spinal cord. These results suggest that MK-4 produces therapeutic effect on ICH by protecting structural integrity of the corticospinal tract.


Assuntos
Hemorragia Cerebral , Tratos Piramidais , Vitamina K 2 , Animais , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Masculino , Vitamina K 2/análogos & derivados , Vitamina K 2/farmacologia , Vitamina K 2/uso terapêutico , Tratos Piramidais/efeitos dos fármacos , Tratos Piramidais/metabolismo , Tratos Piramidais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/tratamento farmacológico
7.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2290-2298, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812129

RESUMO

Ligustilide is the main active component of the volatile oil from Angelica sinensis and Ligusticum chuanxiong in the Umbelliferae family. It is a phthalein compound with anti-inflammatory, analgesic, antioxidant, anti-tumor, anti-atherosclerosis, neuroprotective, and other pharmacological effects. It can improve the permeability of the blood-brain barrier and has important potential in the treatment of neurodegenerative diseases and other nervous system diseases, such as Alzheimer's disease, ischemic stroke, Parkinson's disease, vascular dementia, and depression. Therefore, the mechanism of ligustilide in the treatment of nervous system diseases was summarized to provide a reference for drug development and clinical application.


Assuntos
4-Butirolactona , Doenças do Sistema Nervoso , Humanos , Animais , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , 4-Butirolactona/química , Doenças do Sistema Nervoso/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
8.
CNS Drugs ; 38(6): 425-441, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38724842

RESUMO

In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies are engineered to selectively target FcRn through various methods, such as Fc fragments or monoclonal anti-FcRn antibodies. These approaches enhance the breakdown of autoantibodies by blocking the immunoglobulin G recycling pathway. This mechanism reduces overall plasma immunoglobulin levels, including the levels of pathogenic autoantibodies, without affecting the other immunoglobulin class immunoglobulin A, immunoglobulin E, immunoglobulin M, and immunoglobulin D levels. Drugs that inhibit FcRn include efgartigimod, rozanolixizumab, batoclimab, and nipocalimab. These medications can be administered either intravenously or subcutaneously. Numerous clinical trials are currently underway to investigate their effectiveness, safety, and tolerability in various neurological conditions, including myasthenia gravis and other neurological disorders such as chronic inflammatory demyelinating polyneuropathy, myositis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. Positive results from clinical trials of efgartigimod and rozanolixizumab led to their approval for the treatment of generalized myasthenia gravis. Additional clinical trials are still ongoing. Neonatal Fc receptor inhibitor agents seem to be well tolerated. Reported adverse events include headache (most commonly observed with efgartigimod and rozanolixizumab), upper respiratory tract infection, urinary tract infection, diarrhea, pyrexia, and nausea. Additionally, some of these agents may cause transient hypoalbuminemia and hypercholesterolemia notably reported with batoclimab and nipocalimab. In this review, we discuss the available clinical data for FcRN inhibitor agents in treating different neurological autoimmune diseases.


Assuntos
Antígenos de Histocompatibilidade Classe I , Doenças do Sistema Nervoso , Receptores Fc , Humanos , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/administração & dosagem
9.
Synapse ; 78(4): e22301, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38819491

RESUMO

Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.


Assuntos
Doenças do Sistema Nervoso , Fenilbutiratos , Humanos , Fenilbutiratos/uso terapêutico , Fenilbutiratos/farmacologia , Animais , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo
10.
Acta Paediatr ; 113(6): 1203-1208, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38591640

RESUMO

AIM: Determine the optimal antibiotic choice for lower respiratory tract infection (LRTI) in children with neurodisability. METHODS: Embase, Ovid Emcare and MEDLINE were searched for studies from inception to January 2023. All studies, except case reports, focusing on the antibiotic treatment of LRTI in children, with neurodisabilities were included. Outcomes included length of stay, intensive care admission and mortality. RESULTS: Nine studies met the inclusion criteria (5115 patients). All the studies were of low quality. The shortest length of stay was with anaerobic and gram-positive cover. Five studies used anaerobic, gram-positive and gram-negative cover (e.g., amoxicillin-clavulanic acid), which was frequently adequate. In one large study, it was better than gram-positive and gram-negative cover alone (e.g. ceftriaxone). Those unresponsive or more unwell at presentation improved faster on Pseudomonas aeruginosa cover (e.g., piperacillin-tazobactam). CONCLUSION: In this context, anaerobic, gram-positive and gram-negative cover is just as effective as P. aeruginosa cover, supporting empiric treatment with amoxicillin-clavulanic acid. If there is a failure to improve, broadening to include P. aeruginosa could be considered. This is consistent with a consensus statement on the treatment of LRTI in children with neurodisability. An accepted definition for what constitutes LRTI in this cohort is required before designing prospective randomised trials.


Assuntos
Antibacterianos , Infecções Respiratórias , Humanos , Antibacterianos/uso terapêutico , Criança , Infecções Respiratórias/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico
11.
Redox Biol ; 72: 103138, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581858

RESUMO

The oxytosis/ferroptosis regulated cell death pathway is an emerging field of research owing to its pathophysiological relevance to a wide range of neurological disorders, including Alzheimer's and Parkinson's diseases and traumatic brain injury. Developing novel neurotherapeutics to inhibit oxytosis/ferroptosis offers exciting opportunities for the treatment of these and other neurological diseases. Previously, we discovered cannabinol (CBN) as a unique, potent inhibitor of oxytosis/ferroptosis by targeting mitochondria and modulating their function in neuronal cells. To further elucidate which key pharmacophores and chemical space are essential to the beneficial effects of CBN, we herein introduce a fragment-based drug discovery strategy in conjunction with cell-based phenotypic screens using oxytosis/ferroptosis to determine the structure-activity relationship of CBN. The resulting information led to the development of four new CBN analogs, CP1-CP4, that not only preserve the sub-micromolar potency of neuroprotection and mitochondria-modulating activities seen with CBN in neuronal cell models but also have better druglike properties. Moreover, compared to CBN, the analog CP1 shows improved in vivo efficacy in the Drosophila model of mild traumatic brain injury. Together these studies identify the key molecular scaffolds of cannabinoids that contribute to neuroprotection against oxytosis/ferroptosis. They also highlight the advantageous approach of combining in vitro cell-based assays and rapid in vivo studies using Drosophila models for evaluating new therapeutic compounds.


Assuntos
Canabinol , Descoberta de Drogas , Animais , Humanos , Canabinol/farmacologia , Canabinol/análogos & derivados , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Relação Estrutura-Atividade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Drosophila
12.
J Integr Neurosci ; 23(4): 86, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38682220

RESUMO

Due to the growth of the elderly population, age-related neurological disorders are an increasing problem. Aging begins very gradually and later leads to several neurological issues such as lower neurotransmitter levels, oxidative stress, neuronal inflammation, and continual neuronal loss. These changes might contribute to brain disorders such as Alzheimer's disease (AD), dementia or mild cognitive impairment, and epilepsy and glioma, and can also aggravate these disorders if they were previously present. Momordica charantia (bitter gourd), a member of the Cucurbitaceae family, is a good source of carbohydrates, proteins, vitamins, and minerals. It is used for diabetes and known for its hypoglycemic and antioxidant effects. In this review, we discuss the pharmaceutical effects of M. charantia on age-related neurological disorders. We searched several databases, including PubMed and Google Scholar, using MeSH terms. We searched articles published up until 2022 regardless of publication language. M. charantia is rich in luteolin, which increases acetylcholine in neurons by binding to enzymes in acetylcholine metabolism pathways, including butyrylcholinesterase and acetylcholinesterase. This binding inhibits the hyperphosphorylation of tau protein by restraining its kinase enzyme. Furthermore, this substance can lower serum cholesterol and has multi-target activity in AD and memory loss. M. charantia can also improve memory by decreasing tau protein and it also has potent antioxidant activity and anti-inflammatory effects. This review highlights that M. charantia has effects on many age-related neurological disorders, and can be a cost-effective supplement with minimal side effects.


Assuntos
Momordica charantia , Momordica charantia/química , Humanos , Animais , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Extratos Vegetais/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo
13.
Nutrients ; 16(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674921

RESUMO

OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research. METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search. RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation. CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.


Assuntos
Carnitina , Transtornos Mentais , Doenças do Sistema Nervoso , Humanos , Carnitina/uso terapêutico , Suplementos Nutricionais , Transtornos Mentais/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico
14.
Eur J Med Chem ; 271: 116388, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38614062

RESUMO

Neurological disorders are the leading cause of a large number of mortalities and morbidities. Nitrogen heterocyclic compounds have been pivotal in exhibiting wide array of therapeutic applications. Among them, tetrazole is a ubiquitous class of organic heterocyclic compounds that have attracted much attention because of its unique structural and chemical properties, and a wide range of pharmacological activities comprising anti-convulsant effect, antibiotic, anti-allergic, anti-hypertensive to name a few. Owing to significant chemical and biological properties, the present review aimed at highlighting the recent advances in tetrazole derivatives with special emphasis on their role in the management of neurological diseases. Besides, in-depth structure-activity relationships, molecular docking studies, and associated modes of action of tetrazole derivatives evident in in vitro, in vivo preclinical, and clinical studies have been discussed.


Assuntos
Doenças do Sistema Nervoso , Tetrazóis , Animais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Doenças do Sistema Nervoso/tratamento farmacológico , Relação Estrutura-Atividade , Tetrazóis/química , Tetrazóis/farmacologia , Tetrazóis/síntese química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia
15.
Basic Clin Pharmacol Toxicol ; 134(6): 778-791, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38622813

RESUMO

Neurological disorders (NDs) have a negative impact on the lives of individuals. There could be two explanations for this: unclear aetiology and lack of effective therapy. However, research in the past few years has revealed the role of bio-metals dyshomeostasis in NDs. The imbalance in copper (Cu) concentration may be one of the main causative factors in NDs. In this review, we have discussed the role of Cu in NDs, especially Alzheimer's disease (AD), including the molecular mechanisms involved in Cu-associated NDs like oxidative stress, neuroinflammation, and protein misfolding. We have also summarized the recent Cu-targeting approaches and highlighted the in vitro and in vivo studies recently being reported on the subject. Based on the earlier published reports, it could be speculated that the Cu targeting strategy might be an interesting and potential therapeutic approach for NDs. Various difficulties must be overcome to develop safe and efficient Cu-targeting medications for NDs.


Assuntos
Doença de Alzheimer , Cobre , Doenças do Sistema Nervoso , Estresse Oxidativo , Humanos , Cobre/metabolismo , Animais , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico
16.
Toxins (Basel) ; 16(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38668600

RESUMO

This review discusses the expanding application of botulinum neurotoxin in treating neurological conditions. The article specifically explores novel approaches to using non-paralytic botulinum molecules. These new molecules, such as BiTox or el-iBoNT, offer an alternative for patients who face limitations in using paralytic forms of botulinum neurotoxin due to concerns about muscle function loss. We highlight the research findings that confirm not only the effectiveness of these molecules but also their reduced paralytic effect. We also discuss a potential cause for the diminished paralytic action of these molecules, specifically changes in the spatial parameters of the new botulinum molecules. In summary, this article reviews the current research that enhances our understanding of the application of new botulinum neurotoxins in the context of common conditions and suggests new avenues for developing more efficient molecules.


Assuntos
Toxinas Botulínicas , Humanos , Toxinas Botulínicas/uso terapêutico , Animais , Engenharia de Proteínas , Doenças do Sistema Nervoso/tratamento farmacológico
17.
Expert Opin Drug Discov ; 19(5): 565-585, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38509691

RESUMO

INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.


Assuntos
Caenorhabditis elegans , Modelos Animais de Doenças , Desenvolvimento de Medicamentos , Descoberta de Drogas , Doenças Neurodegenerativas , Caenorhabditis elegans/efeitos dos fármacos , Animais , Humanos , Descoberta de Drogas/métodos , Desenvolvimento de Medicamentos/métodos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Ensaios de Triagem em Larga Escala/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/fisiopatologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia
18.
Phytother Res ; 38(5): 2276-2302, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38424688

RESUMO

Saffron (Crocus sativus), as an herbal medicine, has been extensively investigated for treating neurological and psychiatric disorders. This systematic review aimed to assess the overall effects of saffron on cognition, depression, anxiety, sleep disorders, attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). Relevant randomized controlled trials (RCTs) were identified by searching PubMed/Medline, Web of Science, and Clinical Trials databases up to June 2023 according to search terms and inclusion criteria. The participants were either healthy or suffering from some diseases, including neurological and psychiatric disorders, and consumed saffron or its extracts as an intervention. The risk of bias was assessed according to the Cochrane guidelines, and the PRISMA statement was followed. The meta-analysis was performed using RevMan and STATA software. A random-effects or fixed-effects model was used to calculate the pooled effect sizes. Forty-six RCTs were enrolled, and the duration of these trials ranged from 4 to 48 weeks with saffron or its extracts, both alone or in combination with conventional drugs. Saffron was more effective than placebo in improving cognition, depression with an overall effect size of -4.26 (95% CI: -5.76, -2.77), anxiety of -3.75 (95% CI: -5.83, -1.67), and sleep disorders of -1.91 (95% CI: -2.88, -0.93). Saffron was non-inferior to conventional drugs for treating cognitive disorders, depression, anxiety, ADHD, and OCD, and it exhibited good tolerance with few side effects. Saffron may exert protective roles for neurological and psychiatric disorders and represents a relatively favorable and safe treatment.


Assuntos
Crocus , Extratos Vegetais , Crocus/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos do Sono-Vigília/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Fitoterapia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Depressão/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Ansiedade/tratamento farmacológico
19.
Biomed Pharmacother ; 174: 116487, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518598

RESUMO

Melatonin is a highly conserved molecule produced in the human pineal gland as a hormone. It is known for its essential biological effects, such as antioxidant activity, circadian rhythm regulator, and immunomodulatory effects. The gut is one of the primary known sources of melatonin. The gut microbiota helps produce melatonin from tryptophan, and melatonin has been shown to have a beneficial effect on gut barrier function and microbial population. Dysbiosis of the intestinal microbiota is associated with bacterial imbalance and decreased beneficial microbial metabolites, including melatonin. In this way, low melatonin levels may be related to several human diseases. Melatonin has shown both preventive and therapeutic effects against various conditions, including neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review was aimed to discuss the role of melatonin in the body, and to describe the possible relationship between gut microbiota and melatonin production, as well as the potential therapeutic effects of melatonin on neurological diseases.


Assuntos
Microbioma Gastrointestinal , Melatonina , Doenças do Sistema Nervoso , Melatonina/metabolismo , Melatonina/farmacologia , Humanos , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças do Sistema Nervoso/microbiologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Animais , Disbiose/microbiologia
20.
Cell Biochem Funct ; 42(2): e3964, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38439154

RESUMO

Kaempferol, a flavonoid compound found in various fruits, vegetables, and medicinal plants, has garnered increasing attention due to its potential neuroprotective effects in neurological diseases. This research examines the existing literature concerning the involvement of kaempferol in neurological diseases, including stroke, Parkinson's disease, Alzheimer's disease, neuroblastoma/glioblastoma, spinal cord injury, neuropathic pain, and epilepsy. Numerous in vitro and in vivo investigations have illustrated that kaempferol possesses antioxidant, anti-inflammatory, and antiapoptotic properties, contributing to its neuroprotective effects. Kaempferol has been shown to modulate key signaling pathways involved in neurodegeneration and neuroinflammation, such as the PI3K/Akt, MAPK/ERK, and NF-κB pathways. Moreover, kaempferol exhibits potential therapeutic benefits by enhancing neuronal survival, attenuating oxidative stress, enhancing mitochondrial calcium channel activity, reducing neuroinflammation, promoting neurogenesis, and improving cognitive function. The evidence suggests that kaempferol holds promise as a natural compound for the prevention and treatment of neurological diseases. Further research is warranted to elucidate the underlying mechanisms of action, optimize dosage regimens, and evaluate the safety and efficacy of this intervention in human clinical trials, thereby contributing to the advancement of scientific knowledge in this field.


Assuntos
Doenças do Sistema Nervoso , Fármacos Neuroprotetores , Humanos , Neuroproteção , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Fosfatidilinositol 3-Quinases , Doenças do Sistema Nervoso/tratamento farmacológico
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