Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors

Mazzitelli, Mariacristina; Presto, Peyton; Antenucci, Nico; Meltan, Shakira; Neugebauer, Volker

doi:10.3390/cells11162608

Cited by 16 publications

(10 citation statements)

References 232 publications

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“…Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors that are significant in regulating neurotransmission [ 131 , 132 , 133 ]. GPCRs are membrane-bound proteins expressed in the central nervous system (CNS), and their physiological functions are dependent on their lipid environment [ 134 ].…”

Section: Significance and Interaction Sites Of Cholesterol In Class C...mentioning

confidence: 99%

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

et al. 2023

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G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs; however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of class C GPCRs and speculate on their corresponding therapeutic potential.

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Section: Significance and Interaction Sites Of Cholesterol In Class C...mentioning

confidence: 99%

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

et al. 2023

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“…It exerts its action via the activation of ionotropic and metabotropic receptors. Metabotropic glutamate receptors (mGlu) are G proteincoupled receptors activated by the neurotransmitter glutamate [14] and several studies have highlighted the analgesic potential of these receptors [24,31]. Recently, a subtype of the mGlu receptor family, mGlu 4 , has been identified in the amygdala where it acts as a neuromodulator of sensory and anxiodepressive symptoms associated with persistent inflammatory pain [45].…”

Section: Introductionmentioning

confidence: 99%

Photopharmacological manipulation of amygdala metabotropic glutamate receptor mGlu4 alleviates neuropathic pain

Pereira

Arias

Llebaría

et al. 2023

Pharmacological Research

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“…Metabotropic glutamate receptors (mGluR) are G-protein coupled receptors activated by the binding of glutamate, the main excitatory neurotransmitter of the nervous system ( 1 ). Eight subtypes of mGluR (mGluR1-8) have been cloned and classified into three groups based on their molecular, pharmacological, and signaling properties ( 1 ). Group I mGluRs, including mGluR1 and mGluR5, are implicated in diverse processes such as learning, memory, epilepsy, and pain ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature

et al. 2023

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BackgroundOnly 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease.ObjectiveWe initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies.MethodsObservational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed.ResultsWe identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease.ConclusionsIn patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.

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Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors

Cited by 16 publications

References 232 publications

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

Cholesterol in Class C GPCRs: Role, Relevance, and Localization

Photopharmacological manipulation of amygdala metabotropic glutamate receptor mGlu4 alleviates neuropathic pain

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature

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