About this Research Topic
Recent research has shed light on the potential impact of Cl- dependent GABAergic and glycinergic inhibitory neurotransmission in the development of various neurological disorders (NDs). The disruption of intracellular Cl- concentration ([Cl-]i), which can result from a malfunction of Cl- transporters, may be a shared pathway for numerous NDs. One crucial molecule that regulates [Cl-] in the central nervous system is a potassium-chloride cotransporter (KCC2) that is found only in neurons and is encoded by the SLC12A5 gene. Over the past few years, several patients carrying different mutations in SLC12A5 have been identified. These patients exhibit varying symptoms, ranging from intellectual disability to severe neurodevelopmental delay accompanied by epilepsy.
These findings establish the importance of perturbed [Cl-]i and/or KCC2 function in the development of NDs and create a unique opportunity for the creation of cellular and animal models to understand the mechanisms behind ND formation and to develop effective treatments.
The aim of this topic is to merge the latest findings from clinical studies and research on SLC12A5-related cases with results obtained from various SLC12A5-related experimental models. This is intended to identify the most crucial characteristics shared by different cases, improve our comprehension of the signaling pathways downstream of KCC2 and/or Cl- homeostasis, and provide an update on recent advancements in the search for effective treatments.
Themes covered by this Research Topic include, but are not limited to:
a) Reports on the latest cases of pathologies that are dependent on SLC12A5.
b) New experimental models that involve modifying the expression of genes that impact
neuronal chloride homeostasis.
c) Experimental studies aimed at comprehending the signaling pathways and molecular
mechanisms that control neuronal Cl- homeostasis and/or the functioning of Cl-
related transporters and ion channels.
d) Reviews, perspectives, and methodologies that highlight new and previously
unreviewed reports of the findings mentioned in sections a, b, and c.
These findings establish the importance of perturbed [Cl-]i and/or KCC2 function in the development of NDs and create a unique opportunity for the creation of cellular and animal models to understand the mechanisms behind ND formation and to develop effective treatments.
The aim of this topic is to merge the latest findings from clinical studies and research on SLC12A5-related cases with results obtained from various SLC12A5-related experimental models. This is intended to identify the most crucial characteristics shared by different cases, improve our comprehension of the signaling pathways downstream of KCC2 and/or Cl- homeostasis, and provide an update on recent advancements in the search for effective treatments.
Themes covered by this Research Topic include, but are not limited to:
a) Reports on the latest cases of pathologies that are dependent on SLC12A5.
b) New experimental models that involve modifying the expression of genes that impact
neuronal chloride homeostasis.
c) Experimental studies aimed at comprehending the signaling pathways and molecular
mechanisms that control neuronal Cl- homeostasis and/or the functioning of Cl-
related transporters and ion channels.
d) Reviews, perspectives, and methodologies that highlight new and previously
unreviewed reports of the findings mentioned in sections a, b, and c.
Keywords: Cl-, epilepsy, neuron, neurodevelopmental disorder, autism, SLC12A5, KCC2, Chloride
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