RT journal article
T1 Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1
A1 García Morales, Victoria
A1 Rodríguez Bey, Guillermo
A1 Gómez Pérez, Laura
A1 Domínguez Vías, Germán
A1 González Forero, David
A1 Portillo Pacheco, Federico Luis
A1 Campos Caro, Antonio
A1 Gento Caro, Ángela
A1 Issaoui, Noura
A1 Soler, Rosa M.
A1 Garcera, Ana
A1 Moreno López, Bernardo
A2 Bioquímica y Biología MolecularMicrobiología, Medicina Preventiva, Salud Pública
AB Disruption in membrane excitability contributes to malfunction and differential vulnerabilityof specific neuronal subpopulations in a number of neurological diseases. The adaptor proteinp11, and background potassium channel TASK1, have overlapping distributions in the CNS.Here, we report that the transcription factor Sp1 controls p11 expression, which impacts onexcitability by hampering functional expression of TASK1. In the SOD1-G93A mouse model ofALS, Sp1-p11-TASK1 dysregulation contributes to increased excitability and vulnerability ofmotor neurons. Interference with either Sp1 or p11 is neuroprotective, delaying neuron lossand prolonging lifespan in this model. Nitrosative stress, a potential factor in human neurodegeneration,stimulated Sp1 expression and human p11 promoter activity, at least in part,through a Sp1-binding site. Disruption of Sp1 or p11 also has neuroprotective effects in atraumatic model of motor neuron degeneration. Together our work suggests the Sp1-p11-TASK1 pathway is a potential target for treatment of degeneration of motor neurons.
PB NATURE PUBLISHING GROUP
SN 2041-1723
YR 2019
FD 2019-08
LK http://hdl.handle.net/10498/21720
UL http://hdl.handle.net/10498/21720
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026