摘要Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.These disorders are caused by axonal degeneration of cortical projection neurons,which disrupts the transmission of signals from these neurons to spinal motor neurons and muscles(Blackstone et al.,2011).Since the discovery of the first HSP gene(SPAST)in 1999,over 80 distinct genetic loci associated with HSP have been identified.How the mutations of these functionally divergent genes specifically result in axonal degeneration of cortical projection neurons remains largely unclear.