A Novel Microfluidic Device-Based Neurite Outgrowth Inhibition Assay Reveals the Neurite Outgrowth-Promoting Activity of Tropomyosin Tpm3.1 in Hippocampal Neurons |
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| Authors: | Holly Stefen Amin Hassanzadeh-Barforoushi Merryn Brettle Sandra Fok Alexandra K Suchowerska Nicodemus Tedla Tracie Barber Majid Ebrahimi Warkiani Thomas Fath |
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| Institution: | 1.Neurodegenerative and Repair Unit, School of Medical Science,UNSW Sydney,Sydney,Australia;2.Neuron Culture Core Facility (NCCF),University of New South Wales,Sydney,Australia;3.School of Mechanical and Manufacturing Engineering,University of New South Wales,Sydney,Australia;4.Cancer Division,Garvan Institute of Medical Research/The Kinghorn Cancer Centre,Sydney,Australia;5.Inflammation Research, School of Medical Sciences,University of New South Wales,Sydney,Australia;6.School of Biomedical Engineering,University of Technology Sydney,Sydney,Australia;7.Institute of Molecular Medicine,Sechenov First Moscow State University,Moscow,Russia;8.Faculty of Medicine and Health Sciences, Dementia Research Centre,Macquarie University,Sydney,Australia |
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| Abstract: | Overcoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics. This study investigates tropomyosin isoform 3.1 (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it is known to influence neurite branching and outgrowth. We designed a microfluidic device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo-66. Results show that neurons, overexpressing hTpm3.1, have an increased propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential target for promoting neurite growth in an inhibitory environment in the central nervous system. |
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