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1.
Gac. méd. Méx ; 155(5): 475-482, Sep.-Oct. 2019. tab, graf
Article Dans Anglais | LILACS | ID: biblio-1286546

Résumé

The superoxide dismutase type 1 (SOD1) gene is the first responsible gene mapped in amyotrophic lateral sclerosis type 1 (ALS1), and it codes for the enzyme SOD1, the function of which is to protect against damage mediated by free radicals deriving from oxygen. Its pathophysiological mechanism in ALS1 is related to ischemia. Several molecular studies of the SOD1 gene show that point mutations are the most frequent. The most common mutations in familial cases are p.A4V, p.I113Y, p.G37R, p.D90A and p.E100G, which account for more than 80% of cases, although intronic mutations have also been described as responsible for ALS1. Sporadic cases are explained by mutations in other genes such as SETX and C9orf72. ALS1 is a complex disease with genetic heterogeneity. On the other hand, familial and sporadic cases have a different etiology, which is explained by molecular heterogeneity and multiple pathogenic mechanisms that lead to ALS1; oxidative stress and ischemia are not the only cause. In Mexico, ALS molecular genetics studies are scarce. Clinical studies show an increase in cytokines such as adipsin in cerebrospinal fluid.


Sujets)
Humains , Superoxide dismutase-1/génétique , Sclérose latérale amyotrophique/génétique , Mutation ponctuelle , Âge de début , Stress oxydatif , Sclérose latérale amyotrophique/enzymologie , Ischémie/complications , Mexique
2.
Arq. neuropsiquiatr ; 68(2): 263-268, Apr. 2010. tab
Article Dans Anglais | LILACS | ID: lil-545925

Résumé

OBJECTIVE: We evaluated the efficacy of oral supplementation with milk whey proteins and modified starch (70 percentWPI:30 percentMS), on nutritional and functional parameters of patients with ALS. METHOD: A prospective randomized double-blind study was performed with 16 ALS patients, divided in two groups, the treatment group received (70 percentWPI:30 percentMS) and the control group received (maltodextrin). They underwent prospective nutritional and functional assessment for 4 months. RESULTS: Patients in the treatment group presented weight gain, increased body mass index (BMI), increased arm muscle area and circumference, higher albumin, white blood cell and total lymphocyte counts, and reduced creatine-kinase, aspartate aminotransferase and alanine aminotransferase. In the control group, biochemical parameters did not change, but weight and BMI declined. CONCLUSION: Our results indicate that the agglomerate 70 percentWPI:30 percentMS may be useful in the nutritional therapy of patients with ALS.


OBJETIVO: Avaliar a eficácia da suplementação nutricional oral com proteínas do soro do leite e amido modificado (70 por centoWPI:30 por centoMS), nos parâmetros nutricionais e funcionais de pacientes com esclerose lateral amiotrófica (ELA). MÉTODO: Foi realizado estudo randomizado duplo-cego, com 16 pacientes com ELA, divididos em dois grupos, um que recebeu 70 por centoWPI:30 por centoMS e um controle que recebeu maltodextrina. Os pacientes foram submetidos a avaliação nutricional e funcional durante quatro meses. RESULTADOS: Nos pacientes que receberam o suplemento 70 por centoWPI:30 por centoMS, foi observado ganho de peso, aumento na contagem de linfócitos e redução de creatina kinase, aspartato aminotransferase and alanina aminotransferase. No grupo controle, os parâmetros bioquímicos não sofreram modificações; no entanto, peso e índice de massa corporal diminuíram. CONCLUSÃO: Nossos resultados indicam que o aglomerado 70 por centoWPI:30 por centoMS pode ser útil na terapia de pacientes com ALS.


Sujets)
Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Sclérose latérale amyotrophique/diétothérapie , Compléments alimentaires , Protéines de lait/administration et posologie , Amidon/administration et posologie , Alanine transaminase/sang , Sclérose latérale amyotrophique/enzymologie , Aspartate aminotransferases/sang , Creatine kinase/sang , Méthode en double aveugle , Numération des lymphocytes , Études prospectives , Prise de poids
3.
Experimental & Molecular Medicine ; : 140-150, 2009.
Article Dans Anglais | WPRIM | ID: wpr-76616

Résumé

A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.


Sujets)
Animaux , Humains , Souris , Sclérose latérale amyotrophique/enzymologie , Axones/anatomopathologie , Modèles animaux de maladie humaine , Ganglions sensitifs des nerfs spinaux/anatomopathologie , Souris transgéniques , Mitochondries/anatomopathologie , Motoneurones/métabolisme , Mutation , Dégénérescence nerveuse/anatomopathologie , Cellules réceptrices sensorielles/anatomopathologie , Moelle spinale/anatomopathologie , Superoxide dismutase/génétique
4.
Experimental & Molecular Medicine ; : 611-617, 2009.
Article Dans Anglais | WPRIM | ID: wpr-10785

Résumé

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Abeta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Abeta binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.


Sujets)
Humains , Séquence d'acides aminés , Peptides bêta-amyloïdes/composition chimique , Sclérose latérale amyotrophique/enzymologie , Apoptose , Lignée cellulaire , Lignée cellulaire tumorale , Données de séquences moléculaires , Mutation ponctuelle , Liaison aux protéines , Motifs et domaines d'intéraction protéique , Superoxide dismutase/génétique
5.
São Paulo; s.n; 10 nov. 2008. 132[6] p. graf, ilus.
Thèse Dans Portugais | LILACS | ID: lil-508064

Résumé

Mutações na enzima Cu,Zn-superóxido dismutase (SOD1) estão associadas a casos familiares de Esclerose Lateral Amiotrófica (ELA), uma doença neurodegenerativa motora fatal. Entretanto, a toxicidade das SOD1s mutantes não está totalmente compreendida. Sabe-se que o desenvolvimento da doença está associado ao acúmulo de lesões oxidativas em biomoléculas, mas o papel da SOD1 neste processo não está claro. Estudos com sistemas modelo são, ainda, necessários para desvendar os mecanismos envolvidos. Para contribuir na compreensão dos mecanismos de danos em DNA promovidos pela SOD1, foram realizados estudos in vitro com SOD1/H2O2/HCO3, e estudos com neuroblastomas em cultura transfectados com SOD1 mutante G93A, característica de ELA. Através da quantificacão de quebras em DNA plasmidial e dos níveis de 8-oxo-7,8-dihidro-2'-desoxiguanosina (8-oxodGuo) e 1,N2-eteno-2'-desoxiguanosina (1,N2 -εdGuo) em DNA de timo de bezerro, concluiu-se que o cobre liberado da SOD1 tem um papel central na formação de lesões no DNA promovidas pela SOD1 na presença de H2O2 e que o bicarbonato pode modular a reatividade do cobre liberado. na compreensão dos mecanismos de danos em DNA promovidos pela SOD1, foram realizados estudos in vitro com SOD1/’H POT.2’ ‘O POT.2’ /HC’O POT. 3-‘, e estudos com neuroblastomas em cultura transfectados com SOD1 mutante G93A, característica de ELA...


Sujets)
Apoptose/génétique , Altération de l'ADN/génétique , Sclérose latérale amyotrophique/enzymologie , Sclérose latérale amyotrophique/génétique , Stress oxydatif/génétique , Radicaux libres , Techniques in vitro , Peroxydation lipidique , Numération cellulaire , Électrophorèse sur gel d'agar , Interprétation statistique de données , Techniques de culture cellulaire/méthodes
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