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1.
Artigo em Alemão | MEDLINE | ID: mdl-33034692

RESUMO

Therapeutic vaccines are intended for the treatment of established diseases by harnessing the patient's own immune system. In this article we discuss therapeutic areas that are of relevance for therapeutic vaccination, i.e., oncology and neurodegenerative diseases. Clinical and regulatory aspects related to the manufacture and clinical use of actively personalized cancer vaccines are thoroughly reviewed. This applies to the regulatory classification of genomic sequencing approaches to identify tumor-specific mutations, combination therapies with checkpoint inhibitors, clinical study designs, and the use of suitable adjuvants and drug substances. Huge amounts of data (big data) are increasingly being generated in the area of personalized therapies; we briefly address the impact and usability of big data in regulatory procedures.


Assuntos
Vacinas Anticâncer , Neoplasias , Doenças Neurodegenerativas , Vacinas Anticâncer/uso terapêutico , Alemanha , Humanos , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/prevenção & controle , Vacinação
2.
J Oleo Sci ; 69(10): 1147-1161, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32908097

RESUMO

To present a systematic review of published studies in databases such as PUBMED, REDALYC, SCIELO, DIALNET, SCOPUS, EBSCO and CONRICYT related to the role-played by the components present in the vegetable oil of grape seed (Vitis vinífera) and the prevention or delay in the onset or progression of neurodegenerative diseases. The analysis of the research revealed that neurodegenerative diseases causes alterations in consciousness or in the nervous system leading to severe damage in neuronal cells, these pathologies are considered gradual and progressive. Various syndromes manifest the degenerative diseases of the nervous system; in some of them the predominant symptom is the progressive dementia. Among the components of the diet that in numerous epidemiological studies have shown an inverse association are vitamins, minerals, carotenoids, polyunsaturated fatty acids and polyphenols, the latter being the ones addressed in this document. There is an important evidence that a nutritional support based on polyunsaturated fatty acids and antioxidants can be applied to subjects with a history of neurodegenerative conditions in order to act as neuroprotectors. This requires the determination of the nutritional benefits of these nutrients or of nutraceuticals for the health of this group of patients.


Assuntos
Extrato de Sementes de Uva/administração & dosagem , Doenças Neurodegenerativas/prevenção & controle , Óleos Vegetais/administração & dosagem , Vitis/química , Animais , Antioxidantes , Terapias Complementares , Ácidos Graxos Insaturados , Extrato de Sementes de Uva/química , Humanos , Fármacos Neuroprotetores , Óleos Vegetais/química , Ratos
3.
J Orthop Sports Phys Ther ; 50(8): 415-417, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32736496

RESUMO

SYNOPSIS: Repeated purposeful heading in soccer has come under increased scrutiny as concerns surrounding the association with long-term neurodegenerative disorders in retired players continue to grow. Although a causal link between heading and brain health has not been established, the "precautionary principle" supports the notion that soccer governing bodies and associations should consider implementing pragmatic strategies that can reduce head impact during purposeful heading in youth soccer while this relationship is being investigated. This Viewpoint discusses the current evidence to support low-risk head impact reduction strategies during purposeful heading to protect young, developing players, and how such strategies could be implemented now while research and debate continue on this topic. J Orthop Sports Phys Ther 2020;50(8):415-417. doi:10.2519/jospt.2020.0608.


Assuntos
Cabeça/fisiologia , Destreza Motora/fisiologia , Futebol/fisiologia , Adolescente , Fatores Etários , Criança , Comportamento Competitivo/fisiologia , Feminino , Humanos , Masculino , Força Muscular , Músculos do Pescoço/fisiologia , Doenças Neurodegenerativas/prevenção & controle , Condicionamento Físico Humano/fisiologia , Fatores de Risco , Futebol/lesões , Equipamentos Esportivos
4.
Adv Exp Med Biol ; 1207: 725-730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671789

RESUMO

Neurodegenerative diseases mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD). It is now found that these diseases may be related to autophagic dysfunction. The mechanism is due to abnormalities in autophagy, which lead to abnormal or misfolded proteins accumulating in the cytoplasm, nucleus, and extracellular inclusion bodies, causing neuronal organelle damage and synaptic dysfunction. Since these diseases are much complex, the effect of monotherapy is not significantly affected. There is still a need to strengthen the study of anti-neurodegenerative drugs. Natural products should be a good source for the new drug discovery since most of natural products are multiple-target compounds. In this chapter, we reviewed some progress on studying resveratrol, curcumin, tripterine, and paeoniflorin. These natural products can eliminate abnormal protein aggregates by regulating autophagy, and thereby these compounds are promising to be used in prevention and treatment of neurodegenerative diseases in the future.


Assuntos
Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Doença de Alzheimer , Humanos , Doença de Huntington , Doenças Neurodegenerativas/prevenção & controle , Doença de Parkinson
5.
Adv Gerontol ; 33(2): 299-306, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32593244

RESUMO

Neurodegenerative diseases are a heterogeneous group of nervous system pathologies. They are found mainly in people of an older age group. The incidence of neurodegenerative diseases is continuously growing due to an increase in the average life expectancy of the population. At the moment, there are no effective and safe treatments for neurodegenerative diseases, which are most often diagnosed at the stage of decompensation, when therapy is ineffective and does not bring positive outcomes. Most of the currently used drugs act only symptomatically. The review provides analyzed data and information about the prospects of using peptide bioregulators as neuroprotectors with high physiological activity and low immunogenicity.


Assuntos
Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Peptídeos/farmacologia , Idoso , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Peptídeos/uso terapêutico
6.
Science ; 368(6491): 620-625, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381719

RESUMO

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse-a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency.


Assuntos
Cobre/metabolismo , Hidrazinas/uso terapêutico , Síndrome dos Cabelos Torcidos/tratamento farmacológico , Animais , Transporte Biológico/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular , Transportador de Cobre 1/genética , Modelos Animais de Doenças , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hidrazinas/farmacologia , Masculino , Síndrome dos Cabelos Torcidos/metabolismo , Síndrome dos Cabelos Torcidos/patologia , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/prevenção & controle , Ratos
7.
Adv Exp Med Biol ; 1195: 77-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468462

RESUMO

Neurodegenerative diseases lead to the death of nerve cells in the brain or the spinal cord. A wide range of diseases are included within the group of neurodegenerative disorders, with the most common ones being dementia, Alzheimer's, and Parkinson's diseases. Millions of older people are suffering from such pathologies. The global increase of life expectancy unavoidably leads to a consequent increase in the number of people who will be at some degree affected by neurodegenerative-related diseases. At this moment, there is no effective therapy or treatment that can reverse the loss of neurons. A growing number of studies highlight the value of the consumption of medical foods, and in particular olive oil, as one of the most important components of the Mediterranean diet. A diet based on extra virgin olive oil seems to contribute toward the lowering of risk of age-related pathologies due to high phenol concentration. The link of a polyphenol found in extra virgin olive oil, namely, tyrosol, with the protein tyrosinase, associated to Parkinson's disease is underlined as a paradigm of affiliation between polyphenols and neurodegenerative disorders.


Assuntos
Doenças Neurodegenerativas/prevenção & controle , Azeite de Oliva/química , Azeite de Oliva/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Dieta Mediterrânea , Humanos , Doenças Neurodegenerativas/dietoterapia , Azeite de Oliva/uso terapêutico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Polifenóis/uso terapêutico
8.
Adv Exp Med Biol ; 1243: 53-68, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297211

RESUMO

Protein homeostasis (Proteostasis) is essential for correct and efficient protein function within the living cell. Among the critical components of the Proteostasis Network (PN) are molecular chaperones that serve widely in protein biogenesis under physiological conditions, and prevent protein misfolding and aggregation enhanced by conditions of cellular stress. For Alzheimer's, Parkinson's, Huntington's diseases and ALS, multiple classes of molecular chaperones interact with the highly aggregation-prone proteins amyloid-ß, tau, α-synuclein, huntingtin and SOD1 to influence the course of proteotoxicity associated with these neurodegenerative diseases. Accordingly, overexpression of molecular chaperones and induction of the heat shock response have been shown to be protective in a wide range of animal models of these diseases. In contrast, for cancer cells the upregulation of chaperones has the undesirable effect of promoting cellular survival and tumor growth by stabilizing mutant oncoproteins. In both situations, physiological levels of molecular chaperones eventually become functionally compromised by the persistence of misfolded substrates, leading to a decline in global protein homeostasis and the dysregulation of diverse cellular pathways. The phenomenon of chaperone competition may underlie the broad pathology observed in aging and neurodegenerative diseases, and restoration of physiological protein homeostasis may be a suitable therapeutic avenue for neurodegeneration as well as for cancer.


Assuntos
Chaperonas Moleculares/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Agregação Patológica de Proteínas/prevenção & controle , Proteostase , Animais , Humanos , Doenças Neurodegenerativas/prevenção & controle
9.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098449

RESUMO

Abstract: TFEB (transcription factor EB), which is a master regulator of autophagy and lysosome biogenesis, is considered to be a new therapeutic target for Parkinson's disease (PD). However, only several small-molecule TFEB activators have been discovered and their neuroprotective effects in PD are unclear. In this study, a curcumin derivative, named E4, was identified as a potent TFEB activator. Compound E4 promoted the translocation of TFEB from cytoplasm into nucleus, accompanied by enhanced autophagy and lysosomal biogenesis. Moreover, TFEB knockdown effectively attenuated E4-induced autophagy and lysosomal biogenesis. Mechanistically, E4-induced TFEB activation is mainly through AKT-MTORC1 inhibition. In the PD cell models, E4 promoted the degradation of α-synuclein and protected against the cytotoxicity of MPP+ (1-methyl-4-phenylpyridinium ion) in neuronal cells. Overall, the TFEB activator E4 deserves further study in animal models of neurodegenerative diseases, including PD.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Curcumina/farmacologia , Doenças Neurodegenerativas/metabolismo , Doença de Parkinson/metabolismo , 1-Metil-4-fenilpiridínio/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Células HeLa , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/prevenção & controle , Neurônios/citologia , Neurônios/efeitos dos fármacos , Células PC12 , Doença de Parkinson/genética , Doença de Parkinson/prevenção & controle , Interferência de RNA , Ratos , Transdução de Sinais/efeitos dos fármacos , alfa-Sinucleína/metabolismo
10.
J. negat. no posit. results ; 5(2): 202-211, feb. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194009

RESUMO

Este trabajo describe las virtudes de una investigación centrada en el silicio, uno de los ingredientes más importantes pero menos conocidos de la cerveza, y su acción protectora a nivel neurodegenerativo. Entre los varios factores que contribuyen a la inducción y desarrollo de la enfermedad de Alzheimer, se encuentra el aluminio el cual tiende a concentrarse en el cerebro e inducir, entre otros mecanismos, alteraciones prooxidantes e inflamatorias. El silicio al bloquear esos efectos negativos, se convierte en un ingrediente estrella, que en términos alquimistas sugiere que puede transmutar en oro


This article describes the virtues of a research focused on silicon, one of the most important but least known ingredients in beer, and its protective action at the neurodegenerative level. Among the various factors contributing to the Alzheimer's disease induction and development, aluminum, by concentrating in brain induces, among other mechanisms, pro-oxidant and inflammatory disorders. Silicon, by blocking these negative effects, becomes a star ingredient, which in alchemist terms suggests that has the property to transmute into gold


Assuntos
Humanos , Cerveja/análise , Silício/farmacocinética , Doenças Neurodegenerativas/prevenção & controle , Doença de Alzheimer/prevenção & controle , Fatores de Proteção , Estresse Oxidativo/efeitos dos fármacos , Mediadores da Inflamação/análise , Inflamação/fisiopatologia
11.
Int J Mol Sci ; 21(2)2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947633

RESUMO

Currently available pharmacological treatment of post-ischemia-reperfusion brain injury has limited effectiveness. This review provides an assessment of the current state of neurodegeneration treatment due to ischemia-reperfusion brain injury and focuses on the role of curcumin in the diet. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of curcumin influence on post-ischemic brain damage. Some data on the clinical benefits of curcumin treatment of post-ischemic brain in terms of clinical symptoms and adverse reactions have been reviewed. The data in this review contributes to a better understanding of the potential benefits of curcumin in the treatment of neurodegenerative changes after ischemia and informs scientists, clinicians, and patients, as well as their families and caregivers about the possibilities of such treatment. Due to the pleotropic properties of curcumin, including anti-amyloid, anti-tau protein hyperphosphorylation, anti-inflammatory, anti-apoptotic, and neuroprotective action, as well as increasing neuronal lifespan and promoting neurogenesis, curcumin is a promising candidate for the treatment of post-ischemic neurodegeneration with misfolded proteins accumulation. In this way, it may gain interest as a potential therapy to prevent the development of neurodegenerative changes after cerebral ischemia. In addition, it is a safe substance and inexpensive, easily accessible, and can effectively penetrate the blood-brain barrier and neuronal membranes. In conclusion, the evidence available in a review of the literature on the therapeutic potential of curcumin provides helpful insight into the potential clinical utility of curcumin in the treatment of neurological neurodegenerative diseases with misfolded proteins. Therefore, curcumin may be a promising supplementary agent against development of neurodegeneration after brain ischemia in the future. Indeed, there is a rational scientific basis for the use of curcumin for the prophylaxis and treatment of post-ischemic neurodegeneration.


Assuntos
Isquemia Encefálica/complicações , Curcumina/farmacologia , Doenças Neurodegenerativas/etiologia , Fármacos Neuroprotetores/farmacologia , Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Animais , Isquemia Encefálica/metabolismo , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/prevenção & controle , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Agregados Proteicos , Agregação Patológica de Proteínas/tratamento farmacológico , Agregação Patológica de Proteínas/metabolismo , Proteínas tau/metabolismo
12.
Eur J Drug Metab Pharmacokinet ; 45(1): 51-69, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31602595

RESUMO

BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work investigated its excretion, metabolism, and cytochrome P450-based drug-drug interactions (DDIs). METHODS: After intragastric administration of MDHB, the parent drug was assayed in the urine and faeces of mice. Metabolites of MDHB in the urine, faeces, brain, plasma and liver were detected by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A cocktail approach was used to evaluate the inhibition of cytochrome P450 isoforms by MDHB. RESULTS: The cumulative excretion permille of MDHB in the urine and faeces were found to be 0.67 ± 0.31 and 0.49 ± 0.44‰, respectively. A total of 96 metabolites of MDHB were identified, and all IC50 (half-maximal inhibitory concentration) values of MDHB towards cytochrome P450 isoforms were > 100 µM. CONCLUSIONS: The results suggest that MDHB has a low parent drug cumulative excretion percentage and that MDHB has multiple metabolites and is mainly metabolized through the loss of -CH2 and -CO2, the loss of -CH2O, ester bond hydrolysis, the loss of -O and -CO2, isomerization, methylation, sulfate conjugation, the loss of -CH2O and -O and glycine conjugation, glycine conjugation, the loss of two -O groups and alanine conjugation, the loss of -CH2O and -O and glucose conjugation, glucuronidation, glucose conjugation, etc., in vivo. Finally, MDHB has a low probability of cytochrome P450-based DDIs.


Assuntos
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Hidroxibenzoatos/metabolismo , Eliminação Renal/efeitos dos fármacos , Animais , Interações Medicamentosas , Fezes , Hidroxibenzoatos/sangue , Masculino , Camundongos , Estrutura Molecular , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/metabolismo , Isoformas de Proteínas
13.
Am J Physiol Endocrinol Metab ; 318(5): E750-E764, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714795

RESUMO

Mitochondria have an essential function in cell survival due to their role in bioenergetics, reactive oxygen species generation, calcium buffering, and other metabolic activities. Mitochondrial dysfunctions are commonly found in neurodegenerative diseases (NDs), and diabetes is a risk factor for NDs. However, the role of mitochondria in diabetic neurodegeneration is still unclear. In the present study, we review the latest evidence on the role of mitochondrial dysfunctions in the development of diabetes-related NDs and the underlying molecular mechanisms. Hypoglycemic agents, especially metformin, have been proven to have neuroprotective effects in the treatment of diabetes, in which mitochondria could act as one of the underlying mechanisms. Other hypoglycemic agents, including thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, have gained more attention because of their beneficial effects on NDs, presumably by improving mitochondrial function. Our review highlights the notion that mitochondria could be a promising therapeutic target in the treatment of NDs in patients with diabetes.


Assuntos
Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/complicações , Secreção de Insulina/fisiologia , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/metabolismo , Animais , Encéfalo/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Mitocôndrias/patologia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/prevenção & controle
14.
Anat Sci Int ; 95(2): 230-239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31848974

RESUMO

Peripheral neurodegenerative processes are essential for regenerating damaged peripheral nerves mechanically or genetically. Abnormal neurodegenerative processes induce peripheral neurodegenerative diseases via irreversible nerve damage. Carvacrol, a major component in Origanum vulgare, possesses various effects on organisms, such as antibiotic, anti-inflammatory and cytoprotective effects; although transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP canonical 1 (TRPC1), TRP melastatin M7 (TRPM7), and TRP vanilloid 3 (TRPV3) are carvacrol-regulated TRPs, however, effect of carvacrol on the peripheral neurodegenerative process, and its underlying mechanism, remain unclear. Here, we investigated the specificity of carvacrol for TRPM7 in Schwann cells and the regulatory effect of carvacrol on TRPM7-dependent neurodegenerative processes. To construct peripheral nerve degeneration model, we used with a sciatic explant culture and sciatic nerve axotomy. Ex vivo, in vivo sciatic nerves were treated with carvacrol following an assessment of demyelination (ovoid fragmentation) and axonal degradation using morphometric indices. In these models, carvacrol effectively suppressed the morphometric indices, such as stripe, ovoid, myelin, and neurofilament indices during peripheral nerve degeneration. We found that carvacrol significantly inhibited upregulation of TRPM7 in Schwann cells. In this study, our results suggest that carvacrol effectively protects against the peripheral neurodegenerative process via TRPM7-dependent regulation in Schwann cells. Thus, pharmacological use of carvacrol could be helpful to protect against neurodegeneration that occurs with aging and peripheral neurodegenerative diseases, prophylactically.


Assuntos
Cimenos/farmacologia , Cimenos/uso terapêutico , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/prevenção & controle , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/prevenção & controle , Fitoterapia , Proteínas Serina-Treonina Quinases/metabolismo , Células de Schwann/metabolismo , Canais de Cátion TRPM/metabolismo , Células Cultivadas , Cimenos/isolamento & purificação , Humanos , Origanum/química , Células de Schwann/patologia , Nervo Isquiático , Regulação para Cima/efeitos dos fármacos
15.
Arch Biochem Biophys ; 680: 108227, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838118

RESUMO

Adequate dietary intake has a crucial effect on brain health. High fat diet (HFD) rich in saturated fatty acids is linked to obesity and its complications as neurodegeneration via inducing oxidative stress and inflammation. The present study aimed to evaluate the effect of HFD on cerebral cortex in addition to shedding the light on the modulatory role of N-acetylcytsteine (NAC) and its possible underlying biochemical and molecular mechanisms. Twenty eight male Wistar rats were equally and randomly divided into four groups. Group III, and group IV were fed on HFD (45% kcal from fat) for 10 weeks. Group II and group IV were treated with NAC in a dose of 150 mg/kg body weight via intraperitoneal route. Body weight, blood glucose, serum insulin, insulin resistance index, cerebral cortex redox and inflammatory status were evaluated. Cerebral cortex receptor-interacting serine/threonine-protein kinase3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), nod like receptor protein 3 (NLRP3), interleukin (IL)-18 levels were determined by immunoassay. In addition, apoptosis-associated speck-like proteins (ASC) expression by real-time PCR; inducible nitric oxide synthase (iNOS), glial fibrillary activating protein (GFAP) and matrix metalloproteinase-9 (MMP-9) expression by immunohistochemistry were evaluated. NAC supplementation protected against HFD-induced gain of weights, hyperglycemia, and insulin resistance. Furthermore, NAC improved redox and inflammatory status; decreased levels of RIPK3, MLKL, NLRP3, IL-18; down-regulated ASC, iNOS, GFAP and MMP-9 expression; and decreased myeloperoxidase activity in cerebral cortex. NAC could protect against HFD-induced neurodegeneration via improving glycemic status and peripheral insulin resistance, disrupting oxidative stress/neuroinflammation/necroptosis/inflammasome activation axis in cerebral cortex. NAC may represent a promising strategy for conserving brain health against metabolic diseases-induced neurodegeneration.


Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Inflamação/prevenção & controle , Necroptose/efeitos dos fármacos , Doenças Neurodegenerativas/prevenção & controle , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
16.
Biochem Pharmacol ; 173: 113719, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759977

RESUMO

Aging became a priority in medicine due to the rapid increase of elderly population and age-related diseases in the Western countries. Nine hallmarks have been identified based on their alteration during aging and their capacity to increase longevity. The pathways and the molecular mechanisms to improve lifespan and healthspan are controlled by behavioral, pharmacologic and dietary factors, which remain largely unknown. Among them, naturally occurring compounds, such as polyphenols, are considered potential antiaging agents, because of their ability to modulate some of the evolutionarily conserved hallmarks of aging, including oxidative damage, inflammation, cell senescence, and autophagy. Initially, these compounds gained researchers' attention due to their ability to extend the lifespan of simple model organisms. More recently, some of them have been proposed as senolytic agents to protect against age-related disorders, such as cancer, cardiovascular and neurodegenerative diseases. The intent of this review is to present the most validated molecular mechanisms regulating ageing and longevity and critically analyze how selected polyphenols, namely resveratrol, quercetin, curcumin and catechins, can interfere with these mechanisms.


Assuntos
Envelhecimento/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Senescência Celular/efeitos dos fármacos , Neoplasias/prevenção & controle , Doenças Neurodegenerativas/prevenção & controle , Polifenóis/uso terapêutico , Animais , Humanos , Inflamação/prevenção & controle , Longevidade/efeitos dos fármacos , Estrutura Molecular , Polifenóis/química , Polifenóis/classificação
17.
Wiad Lek ; 73(11): 2345-2348, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33454665

RESUMO

OBJECTIVE: The aim: To assess the knowledge of young adults about neurodegenerative diseases and neuroprotective food. PATIENTS AND METHODS: Material and methods: The study was conducted using an anonymous self-constructed questionnaire. 150 people aged 18 - 30 participated in the study, including 69% (n = 104) women and 31% (n = 46) men. RESULTS: Results: Most of the respondents had sufficient or good knowledge of neurodegenerative diseases and neuroprotective nutrition. The obtained results did not depend on gender, place of residence, and age. However, knowledge was influenced by education (p < 0.05; better-educated respondents indicated more correct answers), and the occupation performed (p < 0.05; respondents performing medical professions gave correct answers more often). CONCLUSION: Conclusions: It seems essential to introduce additional school classes in the field of neurodegenerative diseases and neuroprotective nutrition. Only modern nutritional education from an early age can help implement appropriate eating habits in the field of prevention of neurodegenerative diseases and their application in adulthood.


Assuntos
Doenças Neurodegenerativas , Adolescente , Adulto , Escolaridade , Comportamento Alimentar , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Doenças Neurodegenerativas/prevenção & controle , Estado Nutricional , Inquéritos e Questionários , Adulto Jovem
18.
Nutrients ; 11(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817768

RESUMO

Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure to these factors including nutrients during sensitive periods of life could program brain development and have long-lasting effects on mental health. Studies have shown that early nutritional intervention that includes methyl-donors improves cognitive functions throughout life. Choline is a micronutrient and a methyl donor that is required for normal brain growth and development. It plays a pivotal role in maintaining structural and functional integrity of cellular membranes. It also regulates cholinergic signaling in the brain via the synthesis of acetylcholine. Via its metabolites, it participates in pathways that regulate methylation of genes related to memory and cognitive functions at different stages of development. Choline-related functions have been dysregulated in some neurodegenerative diseases suggesting choline role in influencing mental health across the lifespan.


Assuntos
Colina/administração & dosagem , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Colina/metabolismo , Cognição/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Dieta , Suplementos Nutricionais , Epigênese Genética , Epigenômica , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Memória/efeitos dos fármacos , Micronutrientes/administração & dosagem , Micronutrientes/metabolismo , Doenças Neurodegenerativas/patologia , Fármacos Neuroprotetores/metabolismo
19.
Restor Neurol Neurosci ; 37(6): 571-581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31796710

RESUMO

Many ocular diseases (such as glaucoma, diabetic retinopathy, age-related macular degeneration, and traumatic eye injuries) can result in the degeneration of retinal cells and the subsequent loss of vision. Some kinds of treatments, such as drugs, stem cell transplantation and surgery are reported to be effective in certain patients. However, no confirmatively effective, convenient and low-price intervention has been available so far. Physical exercise has been reported to exert neuroprotective effects on several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Studies investigating the potential impacts of exercise on retinal diseases are rapidly emerging. Here we review these up-to-date findings from both human and animal studies, and discuss the possible mechanisms underlying exercise-elicited protection on retina.


Assuntos
Exercício Físico/fisiologia , Neuroproteção/fisiologia , Condicionamento Físico Animal/fisiologia , Retina/fisiologia , Doenças Retinianas/prevenção & controle , Animais , Humanos , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/prevenção & controle , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/tendências , Doenças Retinianas/fisiopatologia
20.
Chem Res Toxicol ; 32(11): 2182-2191, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31638783

RESUMO

Oxidative stress has been documented as one of the significant causes of neurodegenerative diseases. Therefore, antioxidant therapy for the prevention of neurodegenerative diseases seems to be an interesting strategy in drug discovery. The quinoline-based compound, namely 5-nitro-8-quinolinol (NQ), has shown excellent antimicrobial, anticancer, and anti-inflammatory activities. However, its neuroprotective effects and precise molecular mechanisms in human neuronal cells have not been elucidated. In this work, the effects of NQ on cell viability and morphology were evaluated by the MTT assay and microscopic observation. Moreover, the underlying mechanisms of this compound, inducing the survival rate of neuronal cells under oxidative stress, were investigated by reactive oxygen species (ROS) assay, flow cytometry, Western blotting, and immunofluorescence techniques. In addition, the molecular interaction of sirtuin1 (SIRT1) with NQ was constructed using the AutoDock 4.2 program. Interestingly, NQ protected SH-SY5Y cells against H2O2-induced neurotoxicity through scavenging ROS, upregulating the levels of SIRT1 and FOXO3a, increasing the levels of antioxidant enzymes (catalase and superoxide dismutase), promoting antiapoptotic BCL-2 protein expression, and reducing apoptosis. Besides, molecular docking also revealed that NQ interacted satisfactorily with the active site of SIRT1 similar to the resveratrol, which is the SIRT1 activator and strong antioxidant. These findings suggest that NQ prevents oxidative-stress-induced neurodegeneration because of its antioxidant capacity as well as antiapoptotic property through SIRT1-FOXO3a signaling pathway. Thus, NQ might be a drug that could be repurposed for prevention of neurodegeneration.


Assuntos
Reposicionamento de Medicamentos , Doenças Neurodegenerativas/prevenção & controle , Neurônios/efeitos dos fármacos , Nitroquinolinas/farmacologia , Substâncias Protetoras/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteína Forkhead Box O3/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Simulação de Acoplamento Molecular , Neurônios/metabolismo , Neurônios/patologia , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo
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