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1.
Comput Biol Med ; 175: 108536, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701592

RESUMEN

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.


Asunto(s)
Trastornos Mentales , Enfermedades del Sistema Nervioso , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Bases de Datos Farmacéuticas , Bases de Datos Factuales
2.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38731911

RESUMEN

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.


Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo , Descubrimiento de Drogas , Humanos , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Descubrimiento de Drogas/métodos , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Oftalmopatías/tratamiento farmacológico , Oftalmopatías/metabolismo , Fibrosis , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos
3.
CNS Drugs ; 38(6): 425-441, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38724842

RESUMEN

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.


Asunto(s)
Antígenos de Histocompatibilidad Clase I , Enfermedades del Sistema Nervioso , Receptores Fc , Humanos , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/administración & dosificación
4.
Bol. latinoam. Caribe plantas med. aromát ; 23(3): 349-370, mayo 2024. ilus
Artículo en Inglés | LILACS | ID: biblio-1538077

RESUMEN

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.


Asunto(s)
Extractos Vegetales/uso terapéutico , Vitis/química , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico
5.
J Integr Neurosci ; 23(4): 86, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38682220

RESUMEN

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.


Asunto(s)
Momordica charantia , Momordica charantia/química , Humanos , Animales , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Envejecimiento/metabolismo , Extractos Vegetales/farmacología , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo
6.
Eur J Med Chem ; 271: 116388, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38614062

RESUMEN

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.


Asunto(s)
Enfermedades del Sistema Nervioso , Tetrazoles , Animales , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Relación Estructura-Actividad , Tetrazoles/química , Tetrazoles/farmacología , Tetrazoles/síntesis química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología
7.
Basic Clin Pharmacol Toxicol ; 134(6): 778-791, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38622813

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Cobre , Enfermedades del Sistema Nervioso , Estrés Oxidativo , Humanos , Cobre/metabolismo , Animales , Estrés Oxidativo/efectos de los fármacos , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico
8.
Redox Biol ; 72: 103138, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581858

RESUMEN

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.


Asunto(s)
Cannabinol , Descubrimiento de Drogas , Animales , Humanos , Cannabinol/farmacología , Cannabinol/análogos & derivados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/uso terapéutico , Relación Estructura-Actividad , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Drosophila
9.
Acta Paediatr ; 113(6): 1203-1208, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38591640

RESUMEN

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.


Asunto(s)
Antibacterianos , Infecciones del Sistema Respiratorio , Humanos , Antibacterianos/uso terapéutico , Niño , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedades del Sistema Nervioso/tratamiento farmacológico
10.
Toxins (Basel) ; 16(4)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38668600

RESUMEN

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.


Asunto(s)
Toxinas Botulínicas , Humanos , Toxinas Botulínicas/uso terapéutico , Animales , Ingeniería de Proteínas , Enfermedades del Sistema Nervioso/tratamiento farmacológico
11.
Nutrients ; 16(8)2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38674921

RESUMEN

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.


Asunto(s)
Carnitina , Trastornos Mentales , Enfermedades del Sistema Nervioso , Humanos , Carnitina/uso terapéutico , Suplementos Dietéticos , Trastornos Mentales/tratamiento farmacológico , Enfermedades del Sistema Nervioso/tratamiento farmacológico
12.
Expert Opin Drug Discov ; 19(5): 565-585, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38509691

RESUMEN

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.


Asunto(s)
Caenorhabditis elegans , Modelos Animales de Enfermedad , Desarrollo de Medicamentos , Descubrimiento de Drogas , Enfermedades Neurodegenerativas , Caenorhabditis elegans/efectos de los fármacos , Animales , Humanos , Descubrimiento de Drogas/métodos , Desarrollo de Medicamentos/métodos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/fisiopatología , Ensayos Analíticos de Alto Rendimiento/métodos , Evaluación Preclínica de Medicamentos/métodos , Trastornos del Neurodesarrollo/tratamiento farmacológico , Trastornos del Neurodesarrollo/fisiopatología , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/fisiopatología
13.
Phytother Res ; 38(5): 2276-2302, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38424688

RESUMEN

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.


Asunto(s)
Crocus , Extractos Vegetales , Crocus/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Fitoterapia , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , Depresión/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Ansiedad/tratamiento farmacológico
14.
Biomed Pharmacother ; 174: 116487, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38518598

RESUMEN

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.


Asunto(s)
Microbioma Gastrointestinal , Melatonina , Enfermedades del Sistema Nervioso , Melatonina/metabolismo , Melatonina/farmacología , Humanos , Microbioma Gastrointestinal/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades del Sistema Nervioso/microbiología , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Animales , Disbiosis/microbiología
15.
Cell Biochem Funct ; 42(2): e3964, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38439154

RESUMEN

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.


Asunto(s)
Enfermedades del Sistema Nervioso , Fármacos Neuroprotectores , Humanos , Neuroprotección , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Quempferoles/farmacología , Quempferoles/uso terapéutico , Fosfatidilinositol 3-Quinasas , Enfermedades del Sistema Nervioso/tratamiento farmacológico
16.
Neurochem Res ; 49(6): 1603-1615, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38353895

RESUMEN

We aimed to investigate whether the consumption of Egg White Hydrolysate (EWH) acts on nervous system disorders induced by exposure to Cadmium (Cd) in rats. Male Wistar rats were divided into (a) Control (Ct): H2O by gavage for 28 days + H2O (i.p. - 15th - 28th day); (b) Cadmium (Cd): H2O by gavage + CdCl2 - 1 mg/kg/day (i.p. - 15th - 28th day); (c) EWH 14d: EWH 1 g/kg/day by gavage for 14 days + H2O (i.p.- 15th - 28th day); (d) Cd + EWH cotreatment (Cd + EWHco): CdCl2 + EWH for 14 days; (e) EWH 28d: EWH for 28 days; (f) EWHpre + Cd: EWH (1st - 28th day) + CdCl2 (15th - 28th day). At the beginning and the end of treatment, neuromotor performance (Neurological Deficit Scale); motor function (Rota-Rod test); ability to move and explore (Open Field test); thermal sensitivity (Hot Plate test); and state of anxiety (Elevated Maze test) were tested. The antioxidant status in the cerebral cortex and the striatum were biochemically analyzed. Cd induces anxiety, and neuromotor, and thermal sensitivity deficits. EWH consumption prevented anxiety, neuromotor deficits, and alterations in thermal sensitivity, avoiding neuromotor deficits both when the administration was performed before or during Cd exposure. Both modes of administration reduced the levels of reactive species, and the lipid peroxidation increased by Cd and improved the striatum's antioxidant capacity. Pretreatment proved to be beneficial in preventing the reduction of SOD activity in the cortex. EWH could be used as a functional food with antioxidant properties capable of preventing neurological damage induced by Cd.


Asunto(s)
Cadmio , Clara de Huevo , Estrés Oxidativo , Ratas Wistar , Animales , Masculino , Estrés Oxidativo/efectos de los fármacos , Cadmio/toxicidad , Clara de Huevo/química , Ratas , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/prevención & control , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología
17.
Peptides ; 174: 171166, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38309582

RESUMEN

Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.


Asunto(s)
Enfermedades del Sistema Nervioso , Vasopresinas , Humanos , Vasopresinas/uso terapéutico , Vasopresinas/metabolismo , Hipotálamo/metabolismo , Hipófisis/metabolismo , Encéfalo/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Receptores de Vasopresinas/metabolismo , Arginina Vasopresina/metabolismo
18.
Int J Med Mushrooms ; 26(2): 11-23, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38421693

RESUMEN

Ganoderic acid A (GAA) is one of the major triterpenoids in Ganoderma lucidum (GL). Accumulating evidence has indicated that GAA demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Here, the effects and mechanisms of GAA in the treatment of neurological disorders were evaluated and discussed through previous research results. By summarizing previous research results, we found that GAA may play a neuroprotective role through various mechanisms: anti-inflammatory, anti-oxidative stress, anti-apoptosis, protection of nerve cells, and regulation of nerve growth factor. Therefore, GAA is a promising natural neuroprotective agent and this review would contribute to the future development of GAA as a novel clinical candidate drug for treating neurological diseases.


Asunto(s)
Ácidos Heptanoicos , Lanosterol/análogos & derivados , Enfermedades del Sistema Nervioso , Fármacos Neuroprotectores , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Lanosterol/farmacología , Lanosterol/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico
19.
Peptides ; 175: 171167, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38325715

RESUMEN

Neuropeptide S (NPS) is a 20 amino acids-containing neuroactive molecule discovered by the reverse pharmacology method. NPS is detected in specific brain regions like the brainstem, amygdala, and hypothalamus, while its receptor (NPSR) is ubiquitously expressed in the central nervous system (CNS). Besides CNS, NPS and NPSR are also expressed in the peripheral nervous system. NPSR is a G-protein coupled receptor that primarily uses Gq and Gs signaling pathways to mediate the actions of NPS. In animal models of Parkinsonism and Alzheimer's disease, NPS exerts neuroprotective effects. NPS suppresses oxidative stress, anxiety, food intake, and pain, and promotes arousal. NPSR facilitates reward, reinforcement, and addiction-related behaviors. Genetic variation and single nucleotide polymorphism in NPSR are associated with depression, schizophrenia, rheumatoid arthritis, and asthma. NPS interacts with several neurotransmitters including glutamate, noradrenaline, serotonin, corticotropin-releasing factor, and gamma-aminobutyric acid. It also modulates the immune system via augmenting pro-inflammatory cytokines and plays an important role in the pathogenesis of rheumatoid arthritis and asthma. In the present review, we discussed the distribution profile of NPS and NPSR, signaling pathways, and their importance in the pathophysiology of various neurological disorders. We have also proposed the areas where further investigations on the NPS system are warranted.


Asunto(s)
Artritis Reumatoide , Asma , Enfermedades del Sistema Nervioso , Neuropéptidos , Animales , Ansiedad , Asma/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/genética , Neuropéptidos/metabolismo , Receptores de Neuropéptido/metabolismo , Humanos
20.
Artif Cells Nanomed Biotechnol ; 52(1): 84-103, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38235991

RESUMEN

Neurological disorders such as neurodegenerative diseases and nervous system tumours affect more than one billion people throughout the globe. The physiological sensitivity of the nervous tissue limits the application of invasive therapies and leads to poor treatment and prognosis. One promising solution that has generated attention is Photodynamic therapy (PDT), which can potentially revolutionise the treatment landscape for neurological disorders. PDT attracted substantial recognition for anticancer efficacy and drug conjugation for targeted drug delivery. This review thoroughly explained the basic principles of PDT, scientific interventions and advances in PDT, and their complicated mechanism in treating brain-related pathologies. Furthermore, the merits and demerits of PDT in the context of neurological disorders offer a well-rounded perspective on its feasibility and challenges. In conclusion, this review encapsulates the significant potential of PDT in transforming the treatment landscape for neurological disorders, emphasising its role as a non-invasive, targeted therapeutic approach with multifaceted applications.


Photodynamic therapy is a promising tool to revolutionise the treatment landscape for neurological disorders.The nexus between photodynamic therapy and biological drug conjugation is best suited for non-invasive neurological disorder treatment.


Asunto(s)
Enfermedades del Sistema Nervioso , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Nanotecnología , Sistemas de Liberación de Medicamentos , Enfermedades del Sistema Nervioso/tratamiento farmacológico
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