2024-03-29T14:24:07Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/624052021-11-22T13:11:31Zcom_10261_81com_10261_5com_10261_22com_10261_1col_10261_334col_10261_275
00925njm 22002777a 4500
dc
Morales-García, José A.
author
Luna Medina, Rosario de
author
Alonso-Gil, Sandra
author
Sanz-SanCristóbal, Marina
author
Palomo, Valle
author
Gil, Carmen
author
Santos, Ángel
author
Martínez, Ana
author
Pérez Castillo, Ana
author
2012
Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase originally identified as a regulator of glycogen metabolism but it also plays a pivotal role in numerous cellular functions, including differentiation, cell cycle regulation, and proliferation. The dentate gyrus of the hippocampus, together with the subventricular zone of the lateral ventricles, is one of the regions in which neurogenesis takes place in the adult brain. Here, using a chemical genetic approach that involves the use of several diverse inhibitors of GSK-3 as pharmacological tools, we show that inhibition of GSK-3 induces proliferation, migration, and differentiation of neural stem cells toward a neuronal phenotype in in vitro studies. Also, we demonstrate that inhibition of GSK-3 with the small molecule NP03112, called tideglusib, induces neurogenesis in the dentate gyrus of the hippocampus of adult rats. Taken together, our results suggest that GSK-3 should be considered as a new target molecule for modulating the production and integration of new neurons in the hippocampus as a treatment for neurodegenerative diseases or brain injury and, consequently, its inhibitors may represent new potential therapeutic drugs in neuroregenerative medicine. © 2012 American Chemical Society.
ACS Chemical Neuroscience 3(11): 963-971 (2012)
http://hdl.handle.net/10261/62405
10.1021/cn300110c
23173075
Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in vitro and in vivo