Logo image
Back
High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
Journal article   Open access   Peer reviewed

High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching

Sara M Blazejewski, Sarah A Bennison, Xiaonan Liu and Kazuhito Toyo-Oka
Scientific reports, v 11(1), pp 8156-8156
14 Apr 2021
DOI: https://doi.org/10.1038/s41598-021-87521-3
PMID: 33854138
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/s41598-021-87521-3View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Aurora Kinase A - antagonists & inhibitors Aurora Kinase A - genetics Aurora Kinase B - antagonists & inhibitors Aurora Kinase B - genetics Cell Line Female High-Throughput Screening Assays Loss of Function Mutation Mice Neurites - drug effects Neurites - metabolism Neurites - physiology Neurogenesis Protein Kinase Inhibitors - pharmacology Protein Kinases - genetics Protein Serine-Threonine Kinases - antagonists & inhibitors Protein Serine-Threonine Kinases - genetics Repressor Proteins - antagonists & inhibitors Repressor Proteins - genetics
Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation-a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative disease, and seizures. Investigating the mechanisms underlying neurite formation will allow for identification of potential therapeutics. We used a kinase inhibitor library to screen 493 kinase inhibitors and observed that 45% impacted neuritogenesis in Neuro2a (N-2a) cells. Based on the screening, we further investigated the roles of Aurora kinases A, B, and C and Nuak kinases 1 and 2. The roles of Aurora and Nuak kinases have not been thoroughly studied in the nervous system. Inhibition or overexpression of Aurora and Nuak kinases in primary cortical neurons resulted in various neuromorphological defects, with Aurora A regulating neurite initiation, Aurora B and C regulating neurite initiation and elongation, all Aurora kinases regulating arborization, and all Nuak kinases regulating neurite initiation and elongation and arborization. Our high-throughput screening and analysis of Aurora and Nuak kinases revealed their functions and may contribute to the identification of therapeutics.

Metrics

9 Record Views
19 citations in Web of Science
16 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Neurosciences
Logo image