Effects of MAP4K inhibition on neurite outgrowth.

IF 3.3 3区 医学 Q2 NEUROSCIENCES
Di Ja Lasham, Reza K Arta, Abdul Fuad Hadi, Jun Egawa, Vance P Lemmon, Toshiyuki Takasugi, Michihiro Igarashi, Toshiyuki Someya
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引用次数: 0

Abstract

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.

MAP4K抑制对神经突生长的影响。
蛋白激酶负责蛋白质磷酸化,并参与包括神经元在内的各种细胞的重要细胞内信号转导途径;然而,相当数量的特征不明确的激酶可能参与神经元发育。在这里,我们通过检测一种选择性MAP4K抑制剂PF06260933的作用,考虑了丝裂原激活的蛋白激酶激酶激酶激酶激酶激酶激酶激酶激酶(MAP4Ks)作为神经突生长和突触发生的候选调节因子。与对照组相比,PF06260933处理减少了培养神经元的神经突长度,而不是突触数量,并减少了GAP43和JNK的磷酸化。这些结果表明,MAP4Ks在生理上参与了正常的神经元发育,并且由于MAP4Ks活性降低而导致的神经突生长受损与精神疾病有关。
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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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