Human iPSC-derived sensory neuron platform identifies STE20 kinase inhibitors as neuroprotectants against chemotherapy-induced peripheral neuropathy
By
Clifford J. Woolf1,2,13 Send email to [email protected]
Summary
This article presents a novel high-throughput screening platform using human iPSC-derived sensory neurons to identify neuroprotective compounds against chemotherapy-induced peripheral neuropathy (CIPN). The researchers screened 192 kinase inhibitors and discovered that inhibiting three STE20 kinases—MAP4K4, MINK1, and TNIK—protects against paclitaxel-induced axon degeneration. The findings were validated in both primary human and mouse models, offering a promising therapeutic avenue for preventing this common and dose-limiting side effect of cancer treatment.
Source
bskyHuman iPSC-derived sensory neuron platform identifies STE20 kinase inhibitors as neuroprotectants against chemotherapy-induced peripheral neuropathycell.comKey quotes
· 3 pulledChemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models continues to hinder therapeutic progress.
Here, we establish a scalable and reproducible model of paclitaxel-induced axon degeneration and neurotoxicity in human iPSC-derived sensory neurons, suitable for high-throughput identification of neuroprotective compounds.
Using this platform, we screen a library of 192 kinase inhibitors and identify 19 hits that commonly inhibit three STE20 kinases—MAP4K4, MINK1, and TNIK.
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