TY - JOUR
T1 - Participation of Glutamatergic Ionotropic Receptors in Excitotoxicity
T2 - The Neuroprotective Role of Prolactin
AU - Rodriguez-Chavez, V.
AU - Moran, J.
AU - Molina-Salinas, G.
AU - Zepeda Ruiz, W. A.
AU - Rodriguez, M. C.
AU - Picazo, O.
AU - Cerbon, M.
N1 - Publisher Copyright:
© 2021 IBRO
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Glutamate (Glu) is known as the main excitatory neurotransmitter in the central nervous system. It can trigger a series of processes ranging from synaptic plasticity to neurophysiological regulation. To carry out its functions, Glu acts via interaction with its cognate receptors, which are ligand-dependent. Glutamatergic receptors include ionotropic and metabotropic categories. The first allows the passage of ions through the postsynaptic membrane, while the metabotropic subtype activates signaling cascades through second messengers. It is well known that an excess of extracellular Glu concentration induces overstimulation of ionotropic glutamatergic receptors (iGluRs), causing the excitotoxicity phenomenon that leads to neuronal damage and cell death. Excitotoxicity plays a crucial role in different brain pathologies such as brain strokes, epilepsy and neurodegenerative disorders. However, until now, there are no effective neuroprotective compounds to prevent or rescue neurons from excitotoxicity. Thus, the continuous elucidation of the molecular mechanisms underlying excitotoxicity in order to prevent damage or neuronal death is necessary. Therefore, the aim of this review was to summarize the current knowledge regarding iGluRs, while describing their structures and molecular mechanisms of action, including their role in excitotoxicity, as well as the current strategies to reduce excitotoxic damage. Particularly, strategies mediated by prolactin, a somatotropin family-related hormone that displays a significant neuroprotective effect against both Glu and kainic acid-induced excitotoxicity in the hippocampus, are described. Finally, the role of prolactin as a possible molecule in the treatment of excitotoxicity in neurological diseases is discussed.
AB - Glutamate (Glu) is known as the main excitatory neurotransmitter in the central nervous system. It can trigger a series of processes ranging from synaptic plasticity to neurophysiological regulation. To carry out its functions, Glu acts via interaction with its cognate receptors, which are ligand-dependent. Glutamatergic receptors include ionotropic and metabotropic categories. The first allows the passage of ions through the postsynaptic membrane, while the metabotropic subtype activates signaling cascades through second messengers. It is well known that an excess of extracellular Glu concentration induces overstimulation of ionotropic glutamatergic receptors (iGluRs), causing the excitotoxicity phenomenon that leads to neuronal damage and cell death. Excitotoxicity plays a crucial role in different brain pathologies such as brain strokes, epilepsy and neurodegenerative disorders. However, until now, there are no effective neuroprotective compounds to prevent or rescue neurons from excitotoxicity. Thus, the continuous elucidation of the molecular mechanisms underlying excitotoxicity in order to prevent damage or neuronal death is necessary. Therefore, the aim of this review was to summarize the current knowledge regarding iGluRs, while describing their structures and molecular mechanisms of action, including their role in excitotoxicity, as well as the current strategies to reduce excitotoxic damage. Particularly, strategies mediated by prolactin, a somatotropin family-related hormone that displays a significant neuroprotective effect against both Glu and kainic acid-induced excitotoxicity in the hippocampus, are described. Finally, the role of prolactin as a possible molecule in the treatment of excitotoxicity in neurological diseases is discussed.
KW - excitotoxicity
KW - glutamatergic receptors
KW - neuroprotection
KW - prolactin
UR - http://www.scopus.com/inward/record.url?scp=85102468787&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2021.02.027
DO - 10.1016/j.neuroscience.2021.02.027
M3 - Artículo de revisión
C2 - 33647379
AN - SCOPUS:85102468787
SN - 0306-4522
VL - 461
SP - 180
EP - 193
JO - Neuroscience
JF - Neuroscience
ER -