Image-based Screening Identifies Novel Roles for IκB Kinase and Glycogen Synthase Kinase 3 in Axonal Degeneration
Year: 2011
Type: article
Abstract: Axon degeneration is an active, evolutionarily conserved self-destruction program by which compromised axons fragment in response to varied insults. Unlike programmed cell death, axon degeneration is poorly understood. We have combined robotic liquid handling with automated microscopy and image analysis to create a robust screening platform to measure axon degeneration in mammalian primary neuronal cultures. Using this assay, we performed an unbiased screen of 480 bioactive compounds, identifying 11 that reproducibly delay fragmentation of severed axons in vitro, including two inhibitors of glycogen synthase kinase 3 and two inhibitors of IκB kinase. Knockdown of each of these targets by shRNA lentivirus also delays axon degeneration in vitro, further supporting their role in the axon degeneration program.
Source: Journal of Biological Chemistry
Authors: Josiah Gerdts, Yo Sasaki, Bhupinder Vohra, Jayne Marasa, Jeffrey Milbrandt
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G1114310655, G1389837536, G1820417268, G1946959824, G2025301497, REGULATION OF AXONAL DEGENERATION BY THE DLK KINASE, G6120206497, G6421749520, G670607415, G758343326, G8242737674, G9000006824, G9000032081, G9000063882, G9000282729, G9000316580, G9000319192, Compromised LDH activity causes motor deficits and hastens ALS progression, Cancer Center Support Grant, IDENTIFYING THE NMNAT AXON PROTECTION PATHWAY VIA MULTIPLE SCREENING PARADIGMS
OpenAlex ID: W1991978674