掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

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.

DOI： 10.1186/s13041-023-01066-2

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その他リンク： https://link.springer.com/article/10.1186/s13041-023-01066-2/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

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.

DOI： 10.1186/s13041-022-00951-6

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その他リンク： https://link.springer.com/article/10.1186/s13041-022-00951-6/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.psychres.2022.114481

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.rasd.2021.101729

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