Many studies have revealed the central role of mitogen activated protein kinase (MAPK) in the regulation of long-term changes in neuronal plasticity and synaptic function, such as long-term potentiation (LTP) and long-term depression (LTD). With the "one-stop" drug development service platform, Creative Biolabs is devoted to providing customers with a range of technical services about psychiatric disorders.
Introduction to MAPKs
MAPKs are serine and threonine protein kinases expressed in neurons and non-neuronal cells in the mature central nervous system (CNS) in response to various external stimuli (such as growth factors, glutamate and hormones, cellular stress and pathogens), which mediate proliferation, differentiation and cell survival. p38 MAPK is regarded as a stress-induced kinase, which is activated through the Rac-MEKK-MEK3/6 pathway. Depending on the environment in which MAPKs are activated, they perform specific biological functions that can be used for therapeutic.
Fig.1 Diverse roles of p38 MAPK. (Lee, 2017)
The Relationship Between MAP Kinase and Glutamate Receptors
Glutamate receptors are densely expressed in a wide area of the developing and adult brain, and actively regulate various synapses and cell activities. Glutamate is a neurotransmitter that easily activates ERK, JNK and p38. Numerous reports have fully recorded this in neurons in various areas of the brain, including the cortex, hippocampus, striatum, cerebellum, and spinal cord. All three subtypes of ionotropic glutamate receptors and three subtypes of mGluR seem to continuously regulate the MAPK pathway in a stimulating manner. Active MAPKs translocate to the nucleus to activate a set of specific transcription factors to promote target gene expression. Then, this glutamate receptor-dependent, MAPK-mediated stimulation-transcription coupling controls the development of various forms of synaptic plasticity related to various normal and abnormal neural activities (including memory and addiction).
Fig.2 Overview of the p38 MAPK signal transduction pathways in neurons, astrocytes, and microglia. (Falcicchia, 2020)
Function of MAP Kinase Inhibitors in Psychiatric Disorder
In the central nervous system (CNS), p38 MAPK is highly expressed in the region of learning and memory, which may be an important part of higher brain functions. In addition, the activation of this pathway may be related to the occurrence of some psychiatric disorders, such as depression. The activation of p38 MAPK can also reduce the number of dendritic spines, which may be the result of learning and memory impairment after epilepsy. Therefore, p38 MAPK is a promising target for the development of psychotic drugs. Since the prototype p38 inhibitor SB203580 was discovered in 1994, many p38 inhibitors have been developed. Several p38 inhibitors have been tested in vivo in animal models of psychiatric diseases and have been shown to be effective in the treatment of various psychiatric symptoms.
What Can We Do?
Creative Biolabs offers the synthesis and optimization services for a variety of small molecule antagonists to provide new strategies for the treatment of psychiatric disorders. We offer high-quality target construction and custom target screening services to precisely meet different purposes of projects.
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Experienced technical and support teams
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State-of-the-art facilities
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Specialized in target development
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Fast turnover time and competitive pricing
If you are interested in our services, please feel free to contact us for more information.
References
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Lee, J. K., Kim, N. J. Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer’s disease. Molecules. 2017, 22(8): 1287. Distributed under Open Access license CC BY 4.0, without modification.
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Falcicchia, C., et al. Involvement of p38 MAPK in Synaptic Function and Dysfunction. International journal of molecular sciences. 2020, 21(16): 5624. Distributed under Open Access license CC BY 4.0, without modification.
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