Intracellular Signaling Cascades in Nervous System

Introduction of Intracellular Signaling Cascades

Intracellular signaling cascades is responsible for the enhancement and amplification of a signal derived from extracellular and induction of a series of intracellular responses, involving many biological processes, such as transcription, translation, enzyme activation, protein modifications, cellular metabolism, mitosis, and/or apoptosis. Intracellular signaling cascades involve catalytic enzymes or proteins, cellular receptors, intracellular second messengers, kinases, phosphorylation, and dephosphorylation reactions. Intracellular signaling cascades play important roles in many biological processes of the nervous system, such as learning and memory, synaptic plasticity, spine morphology, neural crest cell development, vertebrate neurogenesis, neural patterning, neuronal polarization, and many diseases of the nervous system. Bellowing introduces several important intracellular signaling cascades.

EGFR (Epidermal growth factor receptor)

EGFR is a cell surface receptor possessing a tyrosine kinase activity. The binding of EGFR to its extracellular cell signaling molecules initiates intracellular signal transduction, which regulates the transcription of transcription factors-activated genes through a series of cytoplasmic cascades, and thus participates in cell growth, differentiation, proliferation, and survival. Understanding the expression and signal transduction pathway of EGFR in the nervous system will help to reveal the pathogenesis of some nervous system diseases and provide the basis for clinical treatment.

Fig.1 ErbB receptor dimerization and activation. (Iwakura, 2013)

MAPK (Mitogen-activated protein kinases)

MAPK signaling cascade is one of the important signal transduction systems in cells. It is a common pathway that transmits extracellular stimulus signals to the nucleus and mediates cellular responses. A variety of stimuli such as ischemia, hormones, and cytokines, can cause MAPK activation through MAPK pathway. After nuclear translocation of MAPK, MAPK activates nuclear transcription factors, regulates the expression of stress proteins, promotes the synthesis of related proteins, and responds to extracellular stimuli. MAPK signaling cascades include Ras-ERK pathway, JNK-SAPK pathway, and so on. They are involved in abnormal brain development, apoptosis of brain cells, brain injury, and protection of brain injury.

Fig.2 Crosstalk between signaling pathways implicated in pathogenesis of neuropsychiatric diseases. (Williams, 2014)

Rho/Rho Kinase

Rho/Rho kinase signaling pathway is a common signaling pathway in many tissues and cells, which regulates the aggregation state of intracellular microfilaments through kinase cascade reaction and participates in a variety of biological behaviors of cells. The Rho/Rho kinase signaling pathway plays an important role in the pathogenesis of inflammatory demyelinating disease of the central nervous system (CNS). Inhibition of the Rho/Rho-kinase signaling pathway has been shown to act as a neuroprotective role.

Hippo/YAP

Hippo signaling pathway is highly conserved and consists of a series of kinase cascades. It mainly participates in the regulation of cell proliferation, apoptosis, and differentiation through downstream effector molecules YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding Motif) transcriptional coactivators. Recent studies have found that HIPPO/YAP signaling pathway is crucial in the proliferation and differentiation of neural stem cells, the proliferation of neuronal precursor cells, the differentiation and activation of glial cells, the development of myelination as well as the occurrence and development of nervous system diseases.

A variety of intracellular signaling cascades have been found in the nervous system, which participates in many neuronal processes. Please click the below link to learn more.

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References

1. Iwakura, Y.; Nawa, H. et al. ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: Pathological implications in schizophrenia and Parkinson's disease. Frontiers in Cellular Neuroscience. 2013, 7:4.
2. Williams, A. J.; Umemori, H. The best-laid plans go oft awry: synaptogenic growth factor signaling in neuropsychiatric disease. Front. Synaptic Neurosci. 2014.