| Autor: |
Tammy Szu-Yu Ho, J. Tabitha Hees, Zhuqiu Xu, Riki Kawaguchi, Natalia P. Biscola, Daniel G Taub, Kuchuan Chen, Xirui Chen, Lee B. Barrett, Long Cheng, Christopher V. Gabel, Leif A. Havton, Daniel H. Geschwind, Clifford J. Woolf |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.11.02.466937 |
| Popis: |
SummaryCNS neurons do not regenerate after injury, leading to permanent functional deficits. Although sensory and motor neuron axons do regrow after peripheral nerve injury, functional outcome is limited due to the incomplete and slow regrowth. The lack of human-relevant assays suitable for large-scale drug screens has limited neuro-repair therapy discovery. To address this we developed a phenotypic screening strategy using human induced pluripotent stem cell-derived motor neurons to identify axon-regeneration promoting compounds and targets. The screens involve both re-plating human motor neurons on chondroitin sulfate proteoglycans and measuring regeneration responses to laser axotomy in spot cultures, and from them we identified multiple hits that promote injured axon regrowth. The top hit blebbistatin, a non-muscle myosin II inhibitor, accelerated axon regeneration and functional recovery after sciatic nerve injury in vivo. Human “injury in a dish” assays are suitable, therefore, to screen for therapeutic interventions that can induce or accelerate axon regeneration. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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