Calcium Signaling Pathway

The regulation of dendrite development is crucial for the establishment of neuronal circuits in the brain. Apart from providing a better understanding of brain development, studies of dendrite morphogenesis have garnered increasing interest because disturbances in dendrite structure are featured in various neurological diseases, including autism spectrum disorders and mental retardation. Calcium (Ca²⁺) signaling plays an important role in the regulation of dendrite morphogenesis and connectivity in the developing brain. Voltage-sensitive Ca²⁺ channels (VSCCs) and NMDA receptors provide a major mode of Ca²⁺ entry in neurons and trigger downstream signaling cascades that control dendrite development. Ca²⁺ entry via VSCCs is thought to act through transcriptional mechanisms to promote dendrite growth and branching, while Ca²⁺ entry via NMDA receptors may act locally to control dendrite branching and stabilization.

Neurons have sophisticated Ca²⁺ signaling systems which deliver the spatial and temporal Ca²⁺ signals necessary to control multiple neuronal functions. Fast acting voltage-sensitive Ca²⁺ entry mechanisms provide the primary Ca²⁺ signal for cell activation, and there are other Ca²⁺ signals that play a more modulatory role. For instance, the NMDA receptors provide regular pulses of Ca²⁺ that maintain the phenotypic stability of the GABAergic interneurons. The Ins(1,4,5)P3/Ca²⁺ signaling pathway has an essential modulatory role in the ascending arousal system by maintaining the tonic excitatory drive responsible for regulating the activity of neuronal rhythms. Subtle alterations in the function of these modulatory pathways (Figure 1) lead to some of the major neurodegenerative diseases such as bipolar disorder, Alzheimer disease (AD) and schizophrenia.

Gene-editing methods for reporter knock-in into endogenous promoter sites generation. Figure 1. Dysregulation of modulatory Ca²⁺ signaling pathways contributes to neural diseases.

The hypothesis that neurodegenerative diseases are caused by Ca²⁺ dysregulation indicates that novel therapies designed to normalize Ca²⁺ signaling pathways could reverse the consequences of neurodegeneration. Such treatments must be fairly subtle and need to concentrate on rectifying the different defects, such as lowering the resting level of Ca²⁺, without interfering with the normal Ca²⁺ signaling pathways. There already is some evidence, based primarily on AD mouse models, that the deleterious effects of excess Ca²⁺ can be reversed by adjusting either the levels of Ca²⁺ or its downstream signaling events using treatments such as Bcl-2, Li+, FK506 and vitamin D.

Creative Biogene is able to offer a variety of calcium signaling pathway related products including stable cell lines, viral particles and clones for your drug discovery projects.

Calcium Signaling Pathway Product Panel

ATP2B1	CALM3	CAMK2G	EGFR	ERBB2	ERBB3
GRIN2D	HTR2A	ITPR1	NOS2	PHKG2	PLCB3
PPIF	PPP3CC	PRKACA	PRKACB	PRKCA	SLC25A5
TBXA2R	VDAC3

References:

Puram SV, et al. A TRPC5-regulated calcium signaling pathway controls dendrite patterning in the mammalian brain. Genes Dev, 2011, 25(24):2659-2673.
Berridge M J. Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia. Prion, 2013, 7(1):2-13.

* For research use only. Not intended for any clinical use.

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