RESUMO
NMDA receptors play an important physiological role in regulating synaptic plasticity, learning and memory. GluN2A subunits are the most abundant functional subunits of NMDA receptors expressed in mature brain, and their dysfunction is related to various neurological diseases. According to subunit composition, GluN2A-containing NMDA receptors can be divided into two types: diheteromeric and triheteromeric receptors. In this review, the expression, functional and pharmacological properties of different kinds of GluN2A-containing NMDA receptors as well as selective GluN2A regulators were described to further understand this type of NMDA receptors.
Assuntos
Plasticidade Neuronal , Receptores de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologiaRESUMO
Much evidence has proved that excitotoxicity induced by excessive release of glutamate contributes largely to damage caused by ischemia. In view of the key role played by NMDA receptors in mediating excitotoxicity, compounds against NMDA receptors signaling pathways have become the most promising type of anti-stroke candidate compounds. However, the limited therapeutic time window for neuroprotection is a key factor preventing NMDA receptor-related compounds from showing efficacy in all clinical trials for ischemic stroke. In this perspective, the determination of therapeutic time windows of these kinds of compounds is useful in ensuring a therapeutic effect and accelerating clinical application. This mini-review discussed the therapeutic time windows of compounds against NMDA receptors signaling pathways, described related influence factors and the status of clinical studies. The purpose of this review is to look for compounds with wide therapeutic time windows and better clinical application prospect.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Humanos , Neuroproteção , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismoRESUMO
Long non-coding RNA (lncRNA), a type of non-protein coding transcripts with lengths exceeding 200 nucleotides, is reported to be widely involved in many cellular and developmental processes. However, few roles of lncRNA in oocyte development have been defined. In this study, to uncover the effect of lncRNA during oocyte maturation, bovine germinal vesicle (GV) and in vitro matured metaphase II (MII) oocytes underwent RNA sequencing. Results revealed a wealth of candidate lncRNAs, which might participate in the biological processes of stage-specific oocytes. Furthermore, their trans- and cis-regulatory effects were investigated in-depth by using bioinformatic software. Functional enrichment analysis of target genes showed that these lncRNAs were likely involved in the regulation of many key signaling pathways during bovine oocyte maturation from GV to MII stage, as well as multiple lncRNA-mRNA networks. One novel lncRNA (MSTRG.19140) was particularly interesting, as it appeared to mediate the regulation of oocyte meiotic resumption, progesterone-mediated oocyte maturation, and cell cycle. Therefore, this study enhanced insights into the regulation of molecular mechanisms of bovine oocyte maturation from a lncRNA-mRNA network perspective.
Assuntos
Redes Reguladoras de Genes/genética , Oócitos/metabolismo , RNA Longo não Codificante/genética , Animais , Bovinos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas de Maturação in Vitro de Oócitos/métodos , Meiose/genética , Metáfase/genética , Oócitos/fisiologia , Oogênese/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismoRESUMO
Long non-coding RNA (lncRNA) is involved in many biological processes, and it has been closely investigated. However, research into the role of lncRNA in ovine ovarian development is scant and poorly understood, particularly in relation to the molecular mechanisms of ovine oocyte maturation. In the current study, RNA sequencing was performed with germinal vesicle (GV) and in vitro matured metaphase II (MII) stage oocytes, isolated from ewes. Through the use of bioinformatic analysis, abundant candidate lncRNAs in stage-specific ovine oocytes were identified, and their trans- and cis-regulatory effects were deeply dissected using computational prediction software. Functional enrichment analysis of these lncRNAs revealed that they were involved in the regulation of many key signaling pathways during ovine oocyte development, which was reflected by their targeted genes. From this study, multiple lncRNA-mRNA networks were presumed to be involved in key signaling pathways regarding ovine oocyte maturation and meiotic resumption. In particular, one novel lncRNA (MSTRG.17927) appeared to mediate the regulation of phosphatidylinositol 3-kinase signaling (PI3K) signaling during ovine oocyte maturation. Therefore, this research offers novel insights into the molecular mechanisms underlying ovine oocyte meiotic maturation regulated by lncRNA-mRNA networks from a genome-wide perspective.