biostudies-literatureWang YCancer Research UKThe Francis Crick InstituteMedical Research CouncilWellcome Trust2554-61https://www.ebi.ac.uk/biostudies/studies/S-EPMC4806223biostudies-literatureUnknown14(11)Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9), a key component of the machinery controlling neurotrophin release, bypasses the need for CSB in neuritogenesis. Importantly, brain-derived neurotrophic factor (BDNF), a neurotrophin implicated in neuronal differentiation and synaptic modulation, and pharmacological mimics such as 7,8-dihydroxyflavone and amitriptyline can compensate for CSB deficiency in cell models of neuronal differentiation as well. SYT9 and BDNF are downrCell reportsPharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation.PMC48062231016611567Muotri AChakravarty PLaposa RRSvejstrup JQJones-Tabah JStewart AWang YfalsePharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation.Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9), a key component of the machinery controlling neurotrophin release, bypasses the need for CSB in neuritogenesis. Importantly, brain-derived neurotrophic factor (BDNF), a neurotrophin implicated in neuronal differentiation and synaptic modulation, and pharmacological mimics such as 7,8-dihydroxyflavone and amitriptyline can compensate for CSB deficiency in cell models of neuronal differentiation as well. SYT9 and BDNF are downr2016-01-01T00:00:00Z2016 Mar2026-05-04T08:53:14.961Z2019-03-27T03:10:12ZS-EPMC48062232697201010.1016/j.celrep.2016.02.051