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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327206 | PMC |
| http://dx.doi.org/10.1186/s13041-022-00951-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Introduction: Neurotrophic factors are widely known for their protective effect on spiral ganglion neurons (SGN) and the protection of these neurons is of great importance to optimize Cochlear Implants, which directly stimulate SGN in deaf patients. Previous studies have identified Cometin - also known as Meteroin-like - to be neuroprotective and beneficial for metabolic disorders. The aim of our study was to investigate the effects of different concentrations of recombinant human Cometin (hCometin) on SGN in regard to neuroprotection and neurite outgrowth and to evaluate its neurite guidance potential using a neurite outgrowth chamber.
View Article and Find Full Text PDFDevelopmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD.
Transl Psychiatry
January 2025
Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea.
Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests.
View Article and Find Full Text PDFAstrocyte-conditional knockout of MOB2 inhibits the phenotypic conversion of reactive astrocytes from A1 to A2 following spinal cord injury in mice.
Int J Biol Macromol
January 2025
Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, People's Republic of China. Electronic address:
After spinal cord injury (SCI), reactive astrocytes in the injured area are triggered after spinal cord injury (SCI) and to polarize into A1 astrocytes with a proinflammatory phenotype or A2 astrocytes with an anti-inflammatory phenotype. Monopolar spindle binder 2 (MOB2) induces astrocyte stellation, maintains cell homeostasis, and promotes neurite outgrowth; however, its role in the phenotypic transformation of reactive astrocytes remains unclear. Here, we confirmed for the first time that MOB2 is associated with A1/A2 phenotypic switching in reactive astrocytes following SCI in mice.
View Article and Find Full Text PDFE46K α-Synuclein Mutation Fails to Promote Neurite Outgrowth by Not Inducing Cdc42EP2 Expression, Unlike Wild-Type or A53T α-Synuclein in SK-N-SH Cells.
Brain Sci
December 2024
Department of Anatomy, College of Medicine, Inje University, Busan 47392, Republic of Korea.
Background/objectives: α-Synuclein (α-syn) protein is a major pathological agent of familial Parkinson's disease (PD), and its levels and aggregations determine neurotoxicity in PD pathogenesis. Although the pathophysiological functions of α-syn have been extensively studied, its biological functions remain elusive, and there are reports of wild-type (WT) α-syn and two missense mutations of α-syn (A30P and A53T) inducing protective neuritogenesis through neurite outgrowth. However, the function of another α-syn mutation, E46K, has not been fully elucidated.
View Article and Find Full Text PDFExosomes: new targets for understanding axon guidance in the developing central nervous system.
Front Cell Dev Biol
January 2025
Key Laboratory of Tropical Translational Medicine and Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China.
Axon guidance is a key event in neural circuit development that drives the correct targeting of axons to their targets through long distances and unique patterns. Exosomes, extracellular vesicles that are smaller than 100 nm, are secreted by most cell types in the brain. Regulation of cell-cell communication, neuroregeneration, and synapse formation by exosomes have been extensively studied.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!