Small Molecule SARM1 Inhibitors Recapitulate the SARM1−/− Phenotype and Allow Recovery of a Metastable Pool of Axons Fated to Degenerate
Robert Hughes, Todd Bosanac, Xianrong Mao, Thomas M. Engber, Aaron DiAntonio, Jeffrey Milbrandt, Rajesh Devraj, Raul Krauss
Abstract
phenotype and protects axons from degeneration induced by axotomy or mitochondrial dysfunction. SARM1 inhibition post-mitochondrial injury with rotenone allows recovery and rescues axons that already entered the metastable state. We conclude that SARM1 inhibition with small molecules has the potential to treat axonopathies of the central and peripheral nervous systems by preventing axonal degeneration and by allowing functional recovery of a metastable pool of damaged, but viable, axons.
Topics & Concepts
Cell biologyAxonal degenerationDegeneration (medical)AxotomyMitochondrionBiologyPhenotypeAxonSmall moleculeCentral nervous systemNeuroscienceBiochemistryPathologyGeneMedicineEndoplasmic Reticulum Stress and DiseaseAutophagy in Disease and TherapyMitochondrial Function and Pathology