RT Journal Article
T1 Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury
A1 Sobrido Cameán, Daniel
A1 Robledo Sánchez, Diego
A1 Romaus-Sanjurjo, Daniel
A1 Pérez Cedrón, Vanessa
A1 Sánchez Piñón, Laura
A1 Rodicio Rodicio, María Celina
A1 Barreiro Iglesias, Antón
K1 Notch
K1 Gamma-secretase
K1 Axon regeneration
K1 GABA
K1 Baclofen
K1 RNA-Seq
K1 Lamprey
K1 Spinal cord injury
AB In a recent study, we showed that GABA and baclofen (a GABAB receptor agonist) inhibit caspase activation and promote axon regeneration in descending neurons of the sea lamprey brainstem after a complete spinal cord injury (Romaus-Sanjurjo et al., 2018a). Now, we repeated these treatments and performed 2 independent Illumina RNA-Sequencing studies in the brainstems of control and GABA or baclofen treated animals. GABA treated larval sea lampreys with their controls were analyzed 29 days after a complete spinal cord injury and baclofen treated larvae with their controls 9 days after the injury. One of the most significantly downregulated genes after both treatments was a HES gene (HESB). HES proteins are transcription factors that are key mediators of the Notch signaling pathway and gamma-secretase activity is crucial for the activation of this pathway. So, based on the RNA-Seq results we subsequently treated spinal cord injured larval sea lampreys with a novel gamma-secretase inhibitor (PF-3804014). This treatment also reduced the expression of HESB in the brainstem and significantly enhanced the regeneration of individually identifiable descending neurons after a complete spinal cord injury. Our results show that gamma-secretase could be a novel target to promote axon regeneration after nervous system injuries
PB Frontiers Media
YR 2020
FD 2020
LK http://hdl.handle.net/10347/21616
UL http://hdl.handle.net/10347/21616
LA eng
NO Sobrido-Cameán D, Robledo D, Romaus-Sanjurjo D, Pérez-Cedrón V, Sánchez L, Rodicio MC and Barreiro-Iglesias A (2020) Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury. Front. Cell Dev. Biol. 8:173
NO Grant sponsors: FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación (Grant number: BFU-2017-87079-P) and the Xunta de Galicia (Grant number: ED431C 2018/28). DR was supported by the BBSRC Institute Strategic Programme Grants to the Roslin Institute (BB/P013732/1, BB/P013740/1, and BB/P013759/1)
DS Minerva
RD 24 abr 2026