Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mol Brain ; 16(1): 79, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980537

RESUMO

Protein kinases are responsible for protein phosphorylation and are involved in important intracellular signal transduction pathways in various cells, including neurons; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), related to as candidate regulators of neurite outgrowth and synaptogenesis, by examining the effects of a selective MAP4K inhibitor PF06260933. PF06260933 treatments of the cultured neurons reduced neurite lengths, not the number of synapses, and phosphorylation of GAP43 and JNK, relative to the control. These results suggest that MAP4Ks are physiologically involved in normal neuronal development and that the resultant impaired neurite outgrowth by diminished MAP4Ks' activity, is related to psychiatric disorders.


Assuntos
Neuritos , Neurônios , Humanos , Neurônios/metabolismo , Neuritos/metabolismo , Transdução de Sinais , Fosforilação , Crescimento Neuronal
2.
Mol Brain ; 15(1): 68, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35883152

RESUMO

Protein kinases are responsible for protein phosphorylation and are involved in important signal transduction pathways; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered cyclin G-associated kinase (GAK) as a candidate regulator of neurite outgrowth and synaptogenesis by examining the effects of the selective GAK inhibitor SGC-GAK-1. SGC-GAK-1 treatment of cultured neurons reduced neurite length and decreased synapse number and phosphorylation of neurofilament 200-kDa subunits relative to the control. In addition, the related kinase inhibitor erlotinib, which has distinct specificity and potency from SGC-GAK-1, had no effect on neurite growth, unlike SGC-GAK-1. These results suggest that GAK may be physiologically involved in normal neuronal development, and that decreased GAK function and the resultant impaired neurite outgrowth and synaptogenesis may be related to neurodevelopmental disorders.


Assuntos
Proteínas Quinases Dependentes de GMP Cíclico , Ciclinas , Proteínas Quinases Dependentes de GMP Cíclico/farmacologia , Ciclina G , Ciclinas/farmacologia , Neuritos , Crescimento Neuronal , Inibidores de Proteínas Quinases/farmacologia , Sinapses
3.
Psychiatry Res ; 310: 114481, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35235885

RESUMO

SETD1A has been identified as a substantial risk gene for schizophrenia. To further investigate the role of SETD1A in the genetic etiology of schizophrenia in the Japanese population, we performed resequencing and association analyses. First, we resequenced the SETD1A coding regions of 974 patients with schizophrenia. Then, we genotyped variants, prioritized via resequencing, in 2,027 patients with schizophrenia and 2,664 controls. Next, we examined the association between SETD1A and schizophrenia in 3,001 patients with schizophrenia and 2,664 controls. Finally, we performed a retrospective chart review of patients with prioritized SETD1A variants. We identified two novel missense variants (p.Ser575Pro and p.Glu857Gln) via resequencing. We did not detect these variants in 4,691 individuals via genotyping. These variants were not significantly associated with schizophrenia in the association analysis. Additionally, we found that a schizophrenia patient with the p.Glu857Gln variant had developmental delays. In conclusion, novel SETD1A missense variants were exclusively identified in Japanese patients with schizophrenia. However, our study does not provide evidence for the contribution of these variants to the genetic etiology of schizophrenia in the Japanese population.


Assuntos
Histona-Lisina N-Metiltransferase , Esquizofrenia , Predisposição Genética para Doença , Histona-Lisina N-Metiltransferase/genética , Humanos , Japão , Mutação de Sentido Incorreto , Estudos Retrospectivos , Esquizofrenia/epidemiologia , Esquizofrenia/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...