RT Journal Article
T1 Protein Kinase C: Targets to Regenerate Brain Injuries?
A1 Geribaldi-Doldan, Noelia
A1 Gomez-Oliva, Ricardo
A1 Dominguez-Garcia, Samuel
A1 Nunez-Abades, Pedro
A1 Castro, Carmen
K1 ADAM17/TACE
K1 Brain injury
K1 Neurogenesis
K1 Neuroregeneration
K1 Protein kinase C
AB Acute or chronic injury to the central nervous system (CNS), causes neuronal death and irreversible cognitive deficits or sensory-motor alteration. Despite the capacity of the adult CNS to generate new neurons from neural stem cells (NSC), neuronal replacement following an injury is a restricted process, which does not naturally result in functional regeneration. Therefore, potentiating endogenous neurogenesis is one of the strategies that are currently being under study to regenerate damaged brain tissue. The insignificant neurogenesis that occurs in CNS injuries is a consequence of the gliogenic/non-neurogenic environment that inflammatory signaling molecules create within the injured area. The modification of the extracellular signals to generate a neurogenic environment would facilitate neuronal replacement. However, in order to generate this environment, it is necessary to unearth which molecules promote or impair neurogenesis to introduce the first and/or eliminate the latter. Specific isozymes of the protein kinase C (PKC) family differentially contribute to generate a gliogenic or neurogenic environment in injuries by regulating the ADAM17 mediated release of growth factor receptor ligands. Recent reports describe several non-tumorigenic diterpenes isolated from plants of the Euphorbia genus, which specifically modulate the activity of PKC isozymes promoting neurogenesis. Diterpenes with 12-deoxyphorbol or lathyrane skeleton, increase NPC proliferation in neurogenic niches in the adult mouse brain in a PKCβ dependent manner exerting their effects on transit amplifying cells, whereas PKC inhibition in injuries promotes neurogenesis. Thus, compounds that balance PKC activity in injuries might be of use in the development of new drugs and therapeutic strategies to regenerate brain injuries.
PB Frontiers Research Foundation
SN 2296-634X
YR 2019
FD 2019-03-04
LK http://hdl.handle.net/10668/13792
UL http://hdl.handle.net/10668/13792
LA en
NO Geribaldi-Doldán N, Gómez-Oliva R, Domínguez-García S, Nunez-Abades P, Castro C. Protein Kinase C: Targets to Regenerate Brain Injuries? Front Cell Dev Biol. 2019 Mar 20;7:39
DS RISalud
RD Apr 17, 2025