biostudies-literatureUnknown14Wali GHereditary spastic paraplegia (HSP) is a group of inherited disorders characterized by progressive spasticity and paralysis of the lower limbs. Autosomal dominant mutations in <i>SPAST</i> gene account for ∼40% of adult-onset patients. We have previously shown that <i>SPAST</i> patient cells have reduced organelle transport and are therefore more sensitive to oxidative stress. To test whether these effects are present in neuronal cells, we first generated 11 induced pluripotent stem (iPS) cell lines from fibroblasts of three healthy controls and three HSP patients with different <i>SPAST</i> mutations. These cells were differentiated into FOXG1-positive forebrain neurons and then evaluated for multiple aspects of axonal transport and fragmentation. Patient neurons exhibited reduced levels Frontiers in neuroscience401https://www.ebi.ac.uk/biostudies/studies/S-EPMC7221066biostudies-literatureOxidative Stress-Induced Axon Fragmentation Is a Consequence of Reduced Axonal Transport in Hereditary Spastic Paraplegia <i>SPAST</i> Patient Neurons.PMC7221066Wali GSutharsan RSue CMMackay-Sim ABlair NFLiyanage EPark JSfalseOxidative Stress-Induced Axon Fragmentation Is a Consequence of Reduced Axonal Transport in Hereditary Spastic Paraplegia <i>SPAST</i> Patient Neurons.Hereditary spastic paraplegia (HSP) is a group of inherited disorders characterized by progressive spasticity and paralysis of the lower limbs. Autosomal dominant mutations in <i>SPAST</i> gene account for ∼40% of adult-onset patients. We have previously shown that <i>SPAST</i> patient cells have reduced organelle transport and are therefore more sensitive to oxidative stress. To test whether these effects are present in neuronal cells, we first generated 11 induced pluripotent stem (iPS) cell lines from fibroblasts of three healthy controls and three HSP patients with different <i>SPAST</i> mutations. These cells were differentiated into FOXG1-positive forebrain neurons and then evaluated for multiple aspects of axonal transport and fragmentation. Patient neurons exhibited reduced levels 2020-01-01T00:00:00Z20202026-05-06T22:28:20.186Z2026-04-07T22:28:07.8ZS-EPMC72210663245756710.3389/fnins.2020.00401