Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators

Niu, Menghan; Yang, Xin; Li, Yuanyuan; Sun, Yanping; Wang, Long; Ha, Jing; Xie, Yinghua; Tian, Changzheng; Wang, Le; Sun, Yongjun

doi:10.1007/s10571-021-01185-1

Cited by 6 publications

(4 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glutamatergic synapses are excitatory synapses closely related to stress. Abnormal levels of N-methyl-D-aspartate (NMDA) receptors are also present in the brain of patients (54,55). Ketamine, a non-competitive NMDA receptors agonist, has been used clinically to treat refractory depression.…”

Section: The Multiple Pathogenesis Of Lldmentioning

confidence: 99%

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

Zhao

Tang³

et al. 2023

Front. Psychiatry

View full text Add to dashboard Cite

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD.

show abstract

Section: The Multiple Pathogenesis Of Lldmentioning

confidence: 99%

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

Zhao

Tang³

et al. 2023

Front. Psychiatry

View full text Add to dashboard Cite

show abstract

“…NMDA receptors are heteromeric ion channels, comprising two obligate NR1 (also called GluN1) subunits, encoded by GRIN1 , and two NR2 (GluN2) subunits (NR2A – NR2D, encoded by GRIN2A - GRIN2D ); they may also include NR3 (GluN3) subunits (encoded by GRIN3A and GRIN3B ). For review, see refs [ 19 , 20 ]. The NR2 subunits contain the glutamate binding site and, via their C-terminal domain (CTD), interact with multiple intracellular proteins such as Ca 2+ /calmodulin-dependent protein kinase II (CamKII), post-synaptic density protein-95 (PSD-95), and Homer.…”

mentioning

confidence: 99%

GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia

Harrison,

Bannerman

2023

Mol Psychiatry

View full text Add to dashboard Cite

Involvement of the glutamate system, particularly N-methyl-D-aspartate (NMDA) receptor hypofunction, has long been postulated to be part of the pathophysiology of schizophrenia. An important development is provided by recent data that strongly implicate GRIN2A, the gene encoding the NR2A (GluN2A) NMDA receptor subunit, in the aetiology of the disorder. Rare variants and common variants are both robustly associated with genetic risk for schizophrenia. Some of the rare variants are point mutations likely affecting channel function, but most are predicted to cause protein truncation and thence result, like the common variants, in reduced gene expression. We review the genomic evidence, and the findings from Grin2a mutant mice and other models which give clues as to the likely phenotypic impacts of GRIN2A genetic variation. We suggest that one consequence of NR2A dysfunction is impairment in a form of hippocampal synaptic plasticity, producing deficits in short-term habituation and thence elevated and dysregulated levels of attention, a phenotype of relevance to schizophrenia and its cognitive aspects.

show abstract

“…The study of GluN2A is therefore more limited due to lack of antagonists selective for this subunit. However, in 2017, a series of compounds were designed based on ACEPC [114], which is a competitive antagonist for the NMDA receptor. Among these compounds, ST3 exhibited Ki values of 52 nM for GluN1/GluN2A receptors and 782 nM for GluN1/GluN2B receptors.…”

Section: Glun2a and Glun2b Nmda Receptor Antagonistsmentioning

confidence: 99%

GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases

Ladagu,

Olopade,

Adejare

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

N-methyl-D-aspartate receptors (NMDARs) are ion channels that respond to the neurotransmitter glutamate, playing a crucial role in the permeability of calcium ions and excitatory neurotransmission in the central nervous system (CNS). Composed of various subunits, NMDARs are predominantly formed by two obligatory GluN1 subunits (with eight splice variants) along with regulatory subunits GluN2 (GluN2A-2D) and GluN3 (GluN3A-B). They are widely distributed throughout the CNS and are involved in essential functions such as synaptic transmission, learning, memory, plasticity, and excitotoxicity. The presence of GluN2A and GluN2B subunits is particularly important for cognitive processes and has been strongly implicated in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. Understanding the roles of GluN2A and GluN2B NMDARs in neuropathologies provides valuable insights into the underlying causes and complexities of major nervous system disorders. This knowledge is vital for the development of selective antagonists targeting GluN2A and GluN2B subunits using pharmacological and molecular methods. Such antagonists represent a promising class of NMDA receptor inhibitors that have the potential to be developed into neuroprotective drugs with optimal therapeutic profiles.

show abstract

Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators

Cited by 6 publications

References 131 publications

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia

GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases

Contact Info

Product

Resources

About