Metamodulation of presynaptic NMDA receptors: New perspectives for pharmacological interventions

Olivero, Guendalina; Grilli, Massimo; Marchi, Mario; Pittaluga, Anna

doi:10.1016/j.neuropharm.2023.109570

Cited by 6 publications

(3 citation statements)

References 261 publications

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“…NMDAR antagonists [15] : These drugs can directly or indirectly block NMDAR activity, thereby reducing calcium influx and excitotoxicity. For example, MK-801, ketamine, and memantine are a class of noncompetitive NMDAR antagonists that bind to the ion channels of the NMDAR and block cation passage; memantine and dextromethorphan are a class of low-affinity noncompetitive NMDAR antagonists that bind to the ion channels of the NMDAR but are effective only in the presence of high levels of glutamate; ifenprodil, Ro25-6981, etc are a class of selective NR2B subunit antagonists, which can bind to the NR2B subunit and inhibit NMDAR in the presence of high levels of NR2B, [92] and AP5, AP7, etc are a class of competitive NMDAR antagonists, which can compete for the glutamate-binding site and prevent glutamate from activating NMDAR. [45] NMDAR modulators: These drugs can improve cerebral IRI by affecting the expression, transport, assembly, and degradation of NMDAR to regulate the amount or function of NMDAR.…”

Section: Pharmacological Intervention Strategies Targeting Nmdar or I...mentioning

confidence: 99%

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Research progress and perspectives of N-methyl-D-aspartate receptor in myocardial and cerebral ischemia-reperfusion injury: A review

Liao,

Wen,

Yang

et al. 2023

Medicine

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There is an urgent need to find common targets for precision therapy, as there are no effective preventive therapeutic measures for combined clinical heart-brain organ protection and common pathways associated with glutamate receptors are involved in heart-brain injury, but current glutamate receptor-related clinical trials have failed. Ischemia-reperfusion injury (IRI) is a common pathological condition that occurs in multiple organs, including the heart and brain, and can lead to severe morbidity and mortality. N-methyl-D-aspartate receptor (NMDAR), a type of ionotropic glutamate receptor, plays a crucial role in the pathogenesis of IRI. NMDAR activity is mainly regulated by endogenous activators, agonists, antagonists, and voltage-gated channels, and activation leads to excessive calcium influx, oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, and necrosis in ischemic cells. In this review, we summarize current research advances regarding the role of NMDAR in myocardial and cerebral IRI and discuss potential therapeutic strategies to modulate NMDAR signaling to prevent and treat IRI.

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Section: Pharmacological Intervention Strategies Targeting Nmdar or I...mentioning

confidence: 99%

“…Several drugs or substances have been found to protect neurons from cerebral IRI by affecting the structure or function of NMDAR. These drugs can be categorized into the following main categories [ 92 ] :…”

Section: Role Of Nmdar In Cerebral Irimentioning

confidence: 99%

Research progress and perspectives of N-methyl-D-aspartate receptor in myocardial and cerebral ischemia-reperfusion injury: A review

Liao,

Wen,

Yang

et al. 2023

Medicine

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“…Another aspect that would deserve further attention is the possibility that anti-GluN autoantibodies can indirectly influence non-NMDA receptors colocalized and functionally associated with the NMDA receptors, altering the mechanism of metamodulation of synaptic transmission [39,95]. This possibility is particularly intriguing since defects or changes in receptor metamodulation are proposed to subserve neuronal vulnerability.…”

Section: Impact Of Anti-nmda Receptor Autoantibodies In Neurons: Futu...mentioning

confidence: 99%

Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic

Olivero,

Roggeri,

Pittaluga

2023

IJMS

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Autoantibodies against NMDA and AMPA receptors have been identified in the central nervous system of patients suffering from brain disorders characterized by neurological and psychiatric symptoms. It has been demonstrated that these autoantibodies can affect the functions and/or the expression of the targeted receptors, altering synaptic communication. The importance to clarify, in preclinical models, the molecular mechanisms involved in the autoantibody-mediated effects has emerged in order to understand their pathogenic role in central disorders, but also to propose new therapeutic approaches for preventing the deleterious central consequences. In this review, we describe some of the available preclinical literature concerning the impact of antibodies recognizing NMDA and AMPA receptors in neurons. This review discusses the cellular events that would support the detrimental roles of the autoantibodies, also illustrating some contrasting findings that in our opinion deserve attention and further investigations before translating the preclinical observations to clinic.

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Progress in metamodulation and receptor-receptor interaction: From physiology to pathology and therapy

2023

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Metamodulation of presynaptic NMDA receptors: New perspectives for pharmacological interventions

Cited by 6 publications

References 261 publications

Research progress and perspectives of N-methyl-D-aspartate receptor in myocardial and cerebral ischemia-reperfusion injury: A review

Research progress and perspectives of N-methyl-D-aspartate receptor in myocardial and cerebral ischemia-reperfusion injury: A review

Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic

Progress in metamodulation and receptor-receptor interaction: From physiology to pathology and therapy

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