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1.
Article in Spanish | LILACS, CUMED | ID: biblio-1280432

ABSTRACT

Introducción: Varias enfermedades neurodegenerativas están asociadas a alteraciones en el metabolismo del folato, lo que tiene sustanciales implicaciones fisiopatológicas, clínicas y terapéuticas potenciales. Objetivo: Reflejar la relevancia del metabolismo del folato para enfermedades neurodegenerativas, destacando su significación fisiopatológica y clínica, y sus implicaciones terapéuticas. Material y métodos: Se consultaron las bases de datos especializadas en busca de artículos publicados hasta marzo de 2020. Se emplearon descriptores específicos y operadores booleanos. Se empleó la estrategia de búsqueda avanzada para la selección de los artículos, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias de asociación entre alteraciones del metabolismo del folato y enfermedades neurodegenerativas. Se han identificado variantes en genes que codifican enzimas involucradas en el metabolismo del folato, y modificaciones en patrones de metilación de ADN, asociadas al riesgo o a la gravedad clínica de las enfermedades de Alzheimer, Parkinson, Huntington, Temblor Esencial y Ataxia Espinocerebelosa tipo 2. Fueron encontradas asociaciones entre enfermedades neurodegenerativas y alteraciones en los niveles de metabolitos del folato, y la frecuencia de micronúcleos. Se han realizado varios estudios observacionales o experimentales que indican que la suplementación con ácido fólico y vitaminas B6 y B12, tiene utilidad terapéutica potencial en el contexto de enfermedades neurodegenerativas. Conclusiones: El metabolismo del folato es de relevancia fisiopatológica, clínica y terapéutica para enfermedades neurodegenerativas. El uso de estrategias dirigidas a restaurar los niveles normales de folatos o de co-factores enzimáticos involucrados en el metabolismo del folato, o a reducir la acumulación de homocisteína, tiene potenciales aplicaciones terapéuticas en el contexto de estas enfermedades(AU)


Introduction: Several neurodegenerative disorders are associated with alterations in folate metabolism, having essential physiopathological, clinical and therapeutic implications. Objective: To assess the relevance of folate metabolism in neurodegenerative disorders, highlighting its physiopathological, clinical and therapeutic significance. Material and Methods: Specialized biomedical databases were searched for studies published up to March 2020. Descriptors and Boolean operators were used. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence of the association between folate metabolism and neurodegenerative disorders were identified. Enzyme-coding genes involved in folate metabolism and epigenetic DNA modifications associated with increased risk or disease severity in Alzheimer´s, Parkinson´s, and Huntington´s diseases, Essential Tremor, and Spinocerebellar ataxia type 2 were also identified. Associations between neurodegenerative disorders and altered levels of folate metabolites and the frequency of micronuclei were found. A number of observational and experimental studies have demonstrated that the supplementation with folic acid and vitamin B6 and B12 has therapeutic potential in the context of neurodegenerative disorders. Conclusions: Folate metabolism is of physiopathological, clinical and therapeutic relevance for neurodegenerative disorders. The use of strategies to normalize folate levels or enzyme cofactors involved in folate metabolism or to reduce homocysteine levels has potential therapeutic applications for these disorders(AU)


Subject(s)
Humans , Severity of Illness Index , DNA , Neurodegenerative Diseases/prevention & control , Spinocerebellar Ataxias , Epigenomics , Clinical Coding , Folic Acid/therapeutic use , Metabolism , Epidemiology, Experimental , Folic Acid/metabolism
2.
Odontol. Clín.-Cient ; 20(2)abr.-maio 2021. ilus
Article in Portuguese | LILACS, BBO | ID: biblio-1369205

ABSTRACT

O objetivo desse trabalho é relatar um caso clínico de tratamento de úlcera traumática labial utilizando protetor bucal em paciente internado em uma Unidade de Terapia Intensiva. Paciente do sexo feminino diagnosticada com uma doença neurodegenerativa apresentou uma lesão de aspecto ulcerado, de aproximadamente 12 mm na mucosa do lábio inferior. O diagnóstico foi de úlcera traumática decorrente de espasmos musculares involuntários em face. O tratamento proposto foi instalação de protetor bucal confeccionado a partir de uma moldeira pré-fabricada de EVA (etil-vinil-acetato) borrachóide associado à medicação tópica a base de corticosteroide sobre a lesão. Após 5 dias foi observada cicatrização completa da úlcera, dispensando o uso do dispositivo. Nos dias seguintes de internação não foram observadas novas lesões. O protetor bucal instalado mostrou-se efetivo no afastamento do tecido traumatizado de novos traumas, protegeu os tecidos não lesionados e proporcionou qualidade de vida e segurança à paciente. Este relato reforça a importância da Odontologia na assistência do paciente crítico... (AU)


The objective of this work is to report a clinical case of treatment of traumatic lip ulcers using mouth guard in a patient admitted to an Intensive Care Unit. Female patient diagnosed with a neurodegenerative disease presented with an ulcerated lesion, of approximately 12 mm in the mucosa of the lower lip. The diagnosis was a traumatic ulcer resulting from involuntary muscle spasms in the face. The proposed treatment was the installation of a mouthguard made from a prefabricated EVA (ethyl vinyl acetate) rubber mold associated with topical corticosteroid medication on the lesion. After 5 days, complete healing oh the ulcer was observed, dispensing with the use of the intraoral device. In the following days of hospitalization, no new injuries were observed. The installed mouthguard proved to be effective in removing traumatized tissue from new traumas, protecting uninjured tissues and providing quality of life and safety to the patient. This report reinforces the importance of Dentistry in the care of critical patients... (AU)


Subject(s)
Humans , Female , Middle Aged , Quality of Life , Neurodegenerative Diseases , Dental Service, Hospital , Intensive Care Units , Lip/injuries , Mouth Protectors , Spasm , Wounds and Injuries , Lip , Mucous Membrane
3.
Dement. neuropsychol ; 15(2): 291-293, Apr.-June 2021. graf
Article in English | LILACS | ID: biblio-1286198

ABSTRACT

ABSTRACT. Brain-damaged patients can develop abnormal attitudes towards their deficits. Misoplegia is one such example, involving exaggerated aversion to an impaired limb, sometimes associated with hatred of paresis and verbal or physical abuse directed at the paretic limb. Few studies or reports on this disorder are available in the literature, prompting the present case report of a patient with misoplegia and vascular dementia.


RESUMO. Pacientes com lesões cerebrais podem apresentar atitudes anormais em relação a seus déficits. Um exemplo é a misoplegia, uma aversão excessiva em relação ao membro com déficit, podendo estar associado a ódio à paralisia e maus tratos verbais ou físicos contra os membros paralisados. Ainda há poucos estudos e relatos sobre esse distúrbio na literatura, evidenciando a importância de um relato de caso de um paciente portador de misoplegia e demência vascular.


Subject(s)
Humans , Dementia , Self-Injurious Behavior , Neurodegenerative Diseases , Mental Disorders
4.
Article in Chinese | WPRIM | ID: wpr-879593

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a relentless, progressive, and presently incurable neurodegenerative disease. Its drug development has been hampered by the lack of effective biomarkers for early diagnosis, progression and prognosis. Recently, significant progress has been made for the identification of body fluid biomarkers for ALS, which conferred both theoretical and practical feasibility for the early diagnosis and progression monitoring. Meanwhile, it also facilitated identification of genes and/or pathways for the pathogenesis of ALS. This review summarized biomarkers identified from cerebrospinal fluid, blood and urine of ALS patients and their clinical implications.


Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Biomarkers , Humans , Neurodegenerative Diseases , Prognosis
5.
Neuroscience Bulletin ; (6): 1735-1744, 2021.
Article in English | WPRIM | ID: wpr-922654

ABSTRACT

Parkinson's disease (PD), the second most common neurodegenerative disease, is clinically characterized by both motor and non-motor symptoms. Although overall great achievements have been made in elucidating the etiology and pathogenesis of PD, the exact mechanisms of this complicated systemic disease are still far from being clearly understood. Consequently, most of the currently-used diagnostic tools and therapeutic options for PD are symptomatic. In this perspective review, we highlight the hot topics in recent PD research for both clinicians and researchers. Some of these hot topics, such as sleep disorders and gut symptoms, have been neglected but are currently emphasized due to their close association with PD. Following these research directions in future PD research may help understand the nature of the disease and facilitate the discovery of new strategies for the diagnosis and therapy of PD.


Subject(s)
Humans , Neurodegenerative Diseases , Parkinson Disease/therapy , Sleep Wake Disorders/therapy
6.
Neuroscience Bulletin ; (6): 1510-1522, 2021.
Article in English | WPRIM | ID: wpr-922641

ABSTRACT

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.


Subject(s)
Alzheimer Disease/therapy , Gastrointestinal Microbiome , Humans , Microbiota , Neurodegenerative Diseases/therapy , Parkinson Disease/therapy
7.
Article in English | WPRIM | ID: wpr-922262

ABSTRACT

Cannabinoid type 1 receptor (CB1R), as the major member of the endocannabinoid system, is among the most abundant receptors expressed in the central nervous system. CB1R is mainly located on the axon terminals of presynaptic neurons and participate in the modulation of neuronal excitability and synaptic plasticity, playing an important role in the pathogenesis of various neuropsychiatric diseases. In recent years, the consistent development of CB1R radioligands and the maturity of molecular imaging techniques, particularly positron emission tomography (PET) may help to visualize the expression and distribution of CB1R in central nervous system . At present, CB1R PET imaging can effectively evaluate the changes of CB1R levels in neuropsychiatric diseases such as Huntington's disease and schizophrenia, and its correlation with the disease severity, therefore providing new insights for the diagnosis and treatment of neuropsychiatric diseases. This article reviews the application of CB1R PET imaging in Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, post-traumatic stress disorder, cannabis use disorder and depression.


Subject(s)
Cannabinoids , Humans , Mental Disorders/diagnostic imaging , Neurodegenerative Diseases/diagnostic imaging , Neurons , Positron-Emission Tomography , Receptor, Cannabinoid, CB1
8.
Article in English | WPRIM | ID: wpr-922251

ABSTRACT

In neuronal system, epigenetic modifications are essential for neuronal development, the fate determination of neural stem cells and neuronal function. The dysfunction of epigenetic regulation is closely related to occurrence and development of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease. Abnormally elevated DNA methylation inhibits the expression of some DNA repair-related genes and affects the progression of Huntington's disease. In the brain of Alzheimer's disease patients, the levels of H3K27ac and H3K9ac histone modifications increased. In addition, the alteration of RNA methylation in animal models of Alzheimer's disease and Parkinson's disease showed discrepancy trends. Therefore, epigenetic modifications may serve as potential therapeutic targets for neurodegenerative diseases. Here, we summarize the recent progress of the roles of epigenetic modifications in neurodegenerative diseases.


Subject(s)
Animals , DNA Methylation , Epigenesis, Genetic , Humans , Neurodegenerative Diseases/genetics , Parkinson Disease/genetics , Protein Processing, Post-Translational
9.
Article in Chinese | WPRIM | ID: wpr-921539

ABSTRACT

Alzheimer's disease(AD)is a chronic neurodegenerative disease whose cause remains unclear.The β-amyloid plaques in the brain are one of the major pathological features of AD.However,the drugs targeting extracellular β-amyloid plaques have failed to cure the disease.Innate immunity and neuroinflammation play a role in the pathogenesis and progression of AD.As the macrophages existing in the central nervous system,microglia are related with extracellular β-amyloid deposition,intracellular neurofibrillary tangle formation,and neuron injury.Accumulating evidence demonstrates that the activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3)inflammasome in microglia plays a role in AD,suggesting new therapeutic target for AD in this signaling pathway.This article reviewed the studies about the activation and regulation of NLRP3 inflammasome in the pathogenesis and progression of AD as well as the development of AD therapies targeting this pathway,aiming to provide reference for further studies in this field.


Subject(s)
Alzheimer Disease , Humans , Inflammasomes , Microglia , NLR Family, Pyrin Domain-Containing 3 Protein , Neurodegenerative Diseases , Nucleotides , Pyrin Domain
10.
Chinese Journal of Biotechnology ; (12): 3812-3819, 2021.
Article in Chinese | WPRIM | ID: wpr-921467

ABSTRACT

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.


Subject(s)
Aged , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Humans , Middle Aged , Neurodegenerative Diseases , Parkinson Disease/therapy
11.
Chinese Journal of Biotechnology ; (12): 3781-3788, 2021.
Article in Chinese | WPRIM | ID: wpr-921464

ABSTRACT

Intestinal microbes have an adjuvant therapeutic effect on neurological disorders (such as Parkinson's, depression, and Alzheimer's disease). It affects brain function and host behavior through the neural pathways, the immune pathways and the microbial metabolites, the so-called gut-brain axis. This article summarizes the recent advances in the role of the microbe-gut-brain axis in neurological disorders, in order to provide new ideas for the treatment of neurodegenerative diseases.


Subject(s)
Brain , Environment , Gastrointestinal Microbiome , Humans , Neurodegenerative Diseases
12.
Journal of Integrative Medicine ; (12): 300-310, 2021.
Article in English | WPRIM | ID: wpr-888763

ABSTRACT

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease. It results from the death of dopaminergic neurons. The pathophysiological mechanisms in idiopathic PD include the production of α-synuclein and mitochondrial respiratory function-affecting complex I, caused by reactive oxygen species. Therefore, the use of natural antioxidants in PD may provide an alternative therapy that prevents oxidative stress and reduces disease progression. In this review, the effects of hydroxytyrosol, Ginkgo biloba, Withania somnifera, curcumin, green tea, and Hypericum perforatum in PD animal and cell line models are compared and discussed. The reviewed antioxidants show evidence of protecting neural cells from oxidative stress in animal and cell models of PD. However, the clinical efficacy of these phytochemicals needs to be optimised and further investigated.


Subject(s)
Animals , Antioxidants/pharmacology , Cell Line , Disease Models, Animal , Models, Animal , Neurodegenerative Diseases , Oxidative Stress , Parkinson Disease/drug therapy
13.
Article in Chinese | WPRIM | ID: wpr-887904

ABSTRACT

Neurodegenerative diseases are associated with neuroinflammation,oxidative stress,and aging,which can lead to cognitive and motor dysfunctions.Recent studies suggest that the development of neurodegenerative diseases is related to adaptive immunity,in which CD4


Subject(s)
Alzheimer Disease , Amyotrophic Lateral Sclerosis , Humans , Neurodegenerative Diseases , Parkinson Disease , T-Lymphocytes
14.
Article in Chinese | WPRIM | ID: wpr-879248

ABSTRACT

The pathogenesis of Alzheimer's disease (AD), a common neurodegenerative disease, is still unknown. It is difficult to determine the atrophy areas, especially for patients with mild cognitive impairment (MCI) at different stages of AD, which results in a low diagnostic rate. Therefore, an early diagnosis model of AD based on 3-dimensional convolutional neural network (3DCNN) and genetic algorithm (GA) was proposed. Firstly, the 3DCNN was used to train a base classifier for each region of interest (ROI). And then, the optimal combination of the base classifiers was determined with the GA. Finally, the ensemble consisting of the chosen base classifiers was employed to make a diagnosis for a patient and the brain regions with significant classification capability were decided. The experimental results showed that the classification accuracy was 88.6% for AD


Subject(s)
Alzheimer Disease/diagnosis , Brain/diagnostic imaging , Cognitive Dysfunction/diagnosis , Early Diagnosis , Humans , Magnetic Resonance Imaging , Neural Networks, Computer , Neurodegenerative Diseases
15.
Article in Chinese | WPRIM | ID: wpr-879088

ABSTRACT

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.


Subject(s)
Alzheimer Disease/genetics , Humans , Medicine, Chinese Traditional , MicroRNAs/genetics , Neurodegenerative Diseases
16.
Acta Physiologica Sinica ; (6): 315-328, 2021.
Article in Chinese | WPRIM | ID: wpr-878260

ABSTRACT

As a member of the Ras superfamily, Rab proteins are small GTP-binding proteins. In the process of endocytosis of macromolecules and substances delivery between organelles, Rab proteins act on vesicle formation, transport, tethering and fusion by recruiting their effectors, therefore being key regulatory factors in vesicle trafficking. Disturbance of localizations and functions of Rab proteins and their effectors are involved in the pathogenesis of several diseases. This review focuses on the main functions of Rab proteins and their possible roles in the onset and progression of neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and Huntington's disease.


Subject(s)
Cell Movement , Endocytosis , Humans , Neurodegenerative Diseases , Protein Transport , rab GTP-Binding Proteins/metabolism
17.
Article in English | WPRIM | ID: wpr-880642

ABSTRACT

Alzheimer's disease (AD) is the most common senile neurodegenerative disease characterized by progressive cognitive dysfunction, psychological and behavioral abnormalities, and impaired ability of activities of daily living. A family with a total of 3 patients were admitted to the Department of Neurology of Xiangya Hospital, Central South University in 2018. The proband showed memory decline as the presenting symptoms, and subsequently showed psychological and behavioral abnormalities, personality changes, seizures, and motor retardation. Definite diagnosis of early-onset familial AD (EOFAD) with missense mutation of presenilin 2 (PSEN2) (c.715A>G p.M239V) was established by whole exome sequencing (WES) technology. We reported the mutation in Chinese Han population for the first time, which expanded the mutation spectrum ofPSEN2 gene and aid to enrich the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Patients with early onset age and complex clinical manifestations of AD can be diagnosed with the help of genetic testing to avoid misdiagnosis.


Subject(s)
Activities of Daily Living , Alzheimer Disease/genetics , Humans , Mutation , Neurodegenerative Diseases , Presenilin-1/genetics , Presenilin-2/genetics
18.
Article in English | WPRIM | ID: wpr-879970

ABSTRACT

Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.


Subject(s)
Amyloid beta-Peptides/metabolism , Humans , Neurodegenerative Diseases , Neuroglia , TRPM Cation Channels/genetics , Transient Receptor Potential Channels
19.
J. venom. anim. toxins incl. trop. dis ; 27: e20210009, 2021. tab, graf, ilus, mapas
Article in English | LILACS, VETINDEX | ID: biblio-1279406

ABSTRACT

Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)


Subject(s)
Animals , Acetylcholinesterase , Spider Venoms/toxicity , Neurotransmitter Agents , Neurodegenerative Diseases , In Vitro Techniques
20.
Rev. méd. Minas Gerais ; 31: 31205, 2021.
Article in English, Portuguese | LILACS | ID: biblio-1291276

ABSTRACT

A Esclerose Lateral Amiotrófica (ELA), uma doença neurodegenerativa fatal, que afeta neurônios motores superiores e inferiores, tem como fisiopatologia mais aceita a excitotoxicidade mediada por glutamato. O atual estudo tem como objetivo estabelecer a relação entre esse neurotransmissor e a ELA, a partir de uma revisão de literatura nas bases de dados Pubmed e Medline. O glutamato é o principal neurotransmissor do Sistema Nervoso Central (SNC) e a excitotoxicidade gerada pelo seu acúmulo nas fendas sinápticas é tida como um dos principais mecanismos envolvidos na fisiopatologia da ELA. Os indivíduos afetados pela ELA apresentam diminuição da expressão de determinados grupos de receptores metabotrópicos de glutamato (mGlu) nos neurônios e nas células da glia desses pacientes. Os mGlu possuem um papel de destaque na modulação da excitotoxicidade por glutamato e são subdivididos em três grupos. Os mGlus do grupo 1 amplificam as transmissões sinápticas excitatórias rápidas, e os dos grupos 2 e 3 atuam como neuroprotetores inibindo a liberação do glutamato na fenda sináptica. Os mGlus são, portanto, considerados alvos terapêuticos para a atuação de drogas que combatem a excitotoxicidade e induzem a produção de fatores neurotróficos, constituindo importante atuação no combate à ELA.


Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease that affects upper and lower motor neurons, has as the most accepted pathophysiology the glutamate-mediated excitotoxicity. The present study aims to establish the relationship between this neurotransmitter and ALS, based on a literature review in the PubMed and Medline databases. Glutamate is the main neurotransmitter of the central nervous system (CNS) and the excitotoxicity generated by its accumulation in the synaptic clefts is considered one of the main mechanisms involved in the pathophysiology of ALS. People affected by ALS present a decrease in expression of certain metabotropic glutamate receptor (mGlu) groups in neurons and glial cells of these patients. mGlu has a prominent role in modulating glutamate excitotoxicity and are subdivided into three groups. Group 1 mGlu amplifies rapid excitatory synaptic transmissions, while groups 2 and 3 act as neuroprotective agents, since among other functions they inhibit glutamate release into the synaptic cleft. Finally, mGlu are considered therapeutic targets for the action of drugs that fight excitotoxicity and induce the production of neurotrophic factors, constituting an important action in the fight against ALS.


Subject(s)
Humans , Receptors, Metabotropic Glutamate , Amyotrophic Lateral Sclerosis , Motor Neuron Disease , Neurotransmitter Agents , Neurodegenerative Diseases , Superoxide Dismutase-1 , Neurotoxins
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