Sandbox Reserved 1160: Difference between revisions
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== Human metabotropic glutamate receptor 5 transmembrane domain == | == Human metabotropic glutamate receptor 5 transmembrane domain == | ||
<StructureSection load='4oo9' size='300' frame='true' side='right' caption='Human metabotropic glutamate receptor 5 transmembrane domain' scene='72/721531/Protien_clean_sce/1'> | <StructureSection load='4oo9' size='300' frame='true' side='right' caption='Human metabotropic glutamate receptor 5 transmembrane domain' scene='72/721531/Protien_clean_sce/1'> | ||
Receiving and responding to extracellular messages is critical to the proper function of the nervous system. Glutamate is the major excitory neurotransmitter of the CNS, and metabotropic glutamate receptor 5 will play a major role in glutamate signaling. Metabotropic glutamate receptor 5 transmembrane domain is a homodimeric GPCR that resides in the cellular membrane <ref name="Dore" />. This domain is a member of the Class C GPCR family and can further be categorized into the Group I subgroup. The transmembrane domain will signal through a Gq/11 pathway. mGlu5 will bind glutamate to the extracellular Venus flytrap domain and the signal will be transduced across the membrane to a heterotrimeric G protein, which will ultimately lead to calcium release and activation of PKC. This will elicit a excitory post-synaptic repose and modulate long term potentiation. Human metabotropic glutamate receptor 5 is found throughout the central nervous system. Areas containing high concentrations of this protein are often involved involved in emotions and higher cognition<ref name="Niswender" />. The localization of mGlu5 in the CNS and the presence of multiple domains makes mGlu5 a possible target for treating schizophrenia, Fragile X, depression, anxiety,and Alzheimer's disease<ref name="Wu" />. | Receiving and responding to extracellular messages is critical to the proper function of the nervous system. Glutamate is the major excitory neurotransmitter of the CNS, and metabotropic glutamate receptor 5 will play a major role in glutamate signaling. Metabotropic glutamate receptor 5 transmembrane domain is a homodimeric [[GPCR]] that resides in the cellular membrane <ref name="Dore" />. This domain is a member of the Class C GPCR family and can further be categorized into the Group I subgroup. The transmembrane domain will signal through a Gq/11 pathway. mGlu5 will bind glutamate to the extracellular Venus flytrap domain and the signal will be transduced across the membrane to a heterotrimeric G protein, which will ultimately lead to calcium release and activation of PKC. This will elicit a excitory post-synaptic repose and modulate long term potentiation. Human metabotropic glutamate receptor 5 is found throughout the central nervous system. Areas containing high concentrations of this protein are often involved involved in emotions and higher cognition<ref name="Niswender" />. The localization of mGlu5 in the CNS and the presence of multiple domains makes mGlu5 a possible target for treating schizophrenia,[http://www.fragilex.org/fragile-x/fragile-x-syndrome/ Fragile X], depression, anxiety,and Alzheimer's disease<ref name="Wu" />. | ||
== Discovery == | == Discovery == | ||
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Fragile X syndrome is the most common genetic cause of mental disabilty, and is a member of the Autism spectrum disorder family<ref name="Bailey" />. The severity of intellectual disability can vary from patient to patient, but symptoms stem from a misregulation of the mGlu1 and MGlu5 pathways<ref name="Bailey" />. This leads to over potentiation in neural cells. Mavoglurant and other allosteric regulators like fenobam have shown promise in treating Fragile X.One positive characteristic of ligands that target the TMD is they tend to be more specific, thus interacting less with brain proteins<ref name="Feng" />. Mavoglurant would act to down regulate glutamate signaling in an attempt to decrease potentiation. Unfortunately, recent Phase 2 clinical trials have proven mavoglurant ineffective <ref name="Bailey" />. Novartis the company who developed the drug has stopped clinical trials of mavoglurant <ref name="Bailey" />. However, modulators of mGlu5 TMD are still be researched to treat Parkinson's, Alzheimer's disease, and various addictions<ref name="Niswender" />. | Fragile X syndrome is the most common genetic cause of mental disabilty, and is a member of the Autism spectrum disorder family<ref name="Bailey" />. The severity of intellectual disability can vary from patient to patient, but symptoms stem from a misregulation of the mGlu1 and MGlu5 pathways<ref name="Bailey" />. This leads to over potentiation in neural cells. Mavoglurant and other allosteric regulators like fenobam have shown promise in treating Fragile X.One positive characteristic of ligands that target the TMD is they tend to be more specific, thus interacting less with brain proteins<ref name="Feng" />. Mavoglurant would act to down regulate glutamate signaling in an attempt to decrease potentiation. Unfortunately, recent Phase 2 clinical trials have proven mavoglurant ineffective <ref name="Bailey" />. Novartis the company who developed the drug has stopped clinical trials of mavoglurant <ref name="Bailey" />. However, modulators of mGlu5 TMD are still be researched to treat Parkinson's, Alzheimer's disease, and various addictions<ref name="Niswender" />. | ||
=== Parkinsons === | === Parkinsons === | ||
== Structural highlights == | == Structural highlights == | ||
