Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing.
Model: Two in vivo models: optic nerve crush with live imaging of acute axonal degeneration, and spinal cord injury by quadrisection of the contralateral spinal cord producing complete transection of the transduced rubrospinal tract, analysed 1 week after lesion; anaesthesia ketamine 95 mg/kg plus xylazine 7 mg/kg or ketamine 75 mg/kg plus medetomidine 0.5 mg/kg
SBI-0206965 at 50 microM gave a significantly higher Axonal Integrity Ratio than control from 4 h after optic nerve crush, whereas 5 microM did not differ from control. ULK1.DN also attenuated long-term axonal degeneration after spinal cord injury, with reduced LC3 and increased p62 puncta indicati…
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