4.2 Review

GRIN2B-related neurodevelopmental disorder: current understanding of pathophysiological mechanisms

Related references

Note: Only part of the references are listed.
Editorial Material Anesthesiology

Opioids and autism spectrum disorder: liaisons dangereuses?

Laszlo Vutskits

Summary: A recent laboratory study examined the effects of repeated exposures of neonatal mice to fentanyl on autism-like behavior, indicating a potential mechanism through opioid receptor-mediated DNA hypermethylation. However, it is still uncertain whether opioid exposure in early life is an independent risk factor for developing autism spectrum disorder in humans due to the challenges of experimental modeling and the subjective nature of diagnosis in human neuropsychiatric disorders. Epidemiological data suggest associations, but further research is needed for a conclusive understanding.

BRITISH JOURNAL OF ANAESTHESIA (2023)

Article Clinical Neurology

L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Ilona Krey et al.

Summary: This study provides evidence that L-serine treatment may improve clinical outcomes in GRIN-related disorders caused by loss-of-function missense variants or null variants.

NEUROTHERAPEUTICS (2022)

Article Neurosciences

Synaptic Dysfunction by Mutations in GRIN2B: Influence of Triheteromeric NMDA Receptors on Gain-of-Function and Loss-of-Function Mutant Classification

Marwa Elmasri et al.

Summary: GRIN2B mutations are associated with severe neurodevelopmental disorders and affect the functional incorporation and decay time of NMDA receptors, depending on the presence of GluN1/2A/2B NMDA receptors.

BRAIN SCIENCES (2022)

Article Anesthesiology

Fentanyl induces autism-like behaviours in mice by hypermethylation of the glutamate receptor gene Grin2b

Zhihao Sheng et al.

Summary: The study found that fentanyl can induce autism-like behaviors in young mice, and this effect occurs through hypermethylation of Grin2b. Blocking the mu-opioid receptor and overexpressing Grin2b can attenuate this effect, while activating the mu-opioid receptor can induce autism-like behaviors.

BRITISH JOURNAL OF ANAESTHESIA (2022)

Review Neurosciences

From bedside-to-bench: What disease-associated variants are teaching us about the NMDA receptor

Johansen B. Amin et al.

Summary: Genetic variations in genes encoding NMDA receptor subunits can be associated with neurodevelopmental, neurological, and psychiatric disorders. Further research on the structure and function of NMDARs is needed to develop a refined pathomechanistic model that can explain the complex machinery regulating NMDARs.

JOURNAL OF PHYSIOLOGY-LONDON (2021)

Article Genetics & Heredity

GRIN database: A unified and manually curated repertoire of GRIN variants

Adrian Garcia-Recio et al.

Summary: This study introduces a database called GRINdb, which gathers genetic, functional, and clinical data from over 4000 GRIN variants, providing a fast and reliable bioinformatics resource for molecular clinical advice. The database allows query and retrieval of reported GRIN variants and reveals important differences in pathogenicity and clinical phenotypes among GRIN variants.

HUMAN MUTATION (2021)

Article Environmental Sciences

DNA methylation at GRIN2B partially mediates the association between prenatal bisphenol F exposure and cognitive functions in 7-year-old children in the SELMA study

Elin Engdahl et al.

Summary: This study demonstrates that prenatal exposure to endocrine disrupting chemical bisphenol F (BPF) is associated with DNA methylation levels at the GRIN2B gene, which in turn affects cognitive functions in 7-year-old children. DNA methylation at specific CpG sites mediates a portion of the association between BPF exposure and cognitive functions, especially in boys.

ENVIRONMENT INTERNATIONAL (2021)

Article Psychiatry

Childhood adversity increases methylation in the GRIN2B gene

Elin Engdahl et al.

Summary: The study shows that childhood adversity is associated with increased methylation levels of GRIN2B in adulthood, indicating sensitivity to early life stress and persistent methylation at this gene. However, no association was found between GRIN2B methylation and depression status.

JOURNAL OF PSYCHIATRIC RESEARCH (2021)

Review Pharmacology & Pharmacy

Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

Kasper B. Hansen et al.

Summary: This study summarizes the physiological effects of L-glutamate and the importance of ionotropic glutamate receptors in brain function. Research on iGluRs has advanced rapidly, particularly in areas such as receptor structure, function, pharmacology, and roles in neurophysiology.

PHARMACOLOGICAL REVIEWS (2021)

Review Cell Biology

Regulation of nonsense-mediated mRNA decay in neural development and disease

Paul Jongseo Lee et al.

Summary: Eukaryotes have evolved various mRNA surveillance mechanisms, with NMD functioning as a quality control mechanism and posttranscriptional gene regulation.

JOURNAL OF MOLECULAR CELL BIOLOGY (2021)

Review Neurosciences

Protein-protein interactions at the NMDA receptor complex: From synaptic retention to synaptonuclear protein messengers

Fabrizio Gardoni et al.

Summary: NMDARs are ion channels in the brain that play essential roles, with different subunits forming various receptor types. They are widely expressed, involved in physiological and pathological processes, and interact with proteins to regulate synaptic activity and cell-wide events affecting gene transcription.

NEUROPHARMACOLOGY (2021)

Article Neurosciences

An Autism-Associated de novo Mutation in GluN2B Destabilizes Growing Dendrites by Promoting Retraction and Pruning

Jacob A. Bahry et al.

Summary: Mutations in the GRIN2B gene lead to autism spectrum disorders, with a GluN2B variant affecting dendrite morphogenesis by shifting branch growth towards retraction. Mutant neurons exhibit increased pruning of dendritic branches despite forming new branches at similar rates to wild-type neurons. This results in a nearly complete elimination of the net expansion of arbor size and complexity during developmental periods.

FRONTIERS IN CELLULAR NEUROSCIENCE (2021)

Article Biology

Two de novo GluN2B mutations affect multiple NMDAR-functions and instigate severe pediatric encephalopathy

Shai Kellner et al.

Summary: This study identified two toddlers with different heterozygous missense mutations in the same glycine residue of the GRIN2B gene, resulting in severely impaired glutamate binding and extreme effects on channel function. The variants exhibit dominant-negative effects on mixed channels and suppress synaptic GluNRs, pointing towards a Loss-of-Function mechanism primarily instigated by LBD mutations in GluN2B.

ELIFE (2021)

Article Clinical Neurology

Recurrent seizure-related GRIN1 variant: Molecular mechanism and targeted therapy

Yuchen Xu et al.

Summary: A variant in the GRIN1 gene was identified in a patient with epilepsy, leading to enhanced agonist potency and sensitivity to certain FDA-approved drugs, ultimately reducing seizure burden. This finding contributes to the understanding of genotype-phenotype correlations and explores therapeutic strategies for treating GRIN1-related neurological conditions.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2021)

Review Biochemistry & Molecular Biology

Regulation of NMDA glutamate receptor functions by the GluN2 subunits

Marta Vieira et al.

JOURNAL OF NEUROCHEMISTRY (2020)

Article Biochemistry & Molecular Biology

Disease-associated GRIN protein truncating variants trigger NMDA receptor loss-of-function

Ana Santos-Gomez et al.

HUMAN MOLECULAR GENETICS (2020)

Article Genetics & Heredity

Epigenetic-mediated N-methyl-D-aspartate receptor changes in the brain of isolated reared rats

Camila Marcelino Loureiro et al.

EPIGENOMICS (2020)

Review Neurosciences

Stages and transitions in dendrite arbor differentiation

Li-Foong Yoong et al.

NEUROSCIENCE RESEARCH (2019)

Review Cell Biology

Quality and quantity control of gene expression by nonsense-mediated mRNA decay

Tatsuaki Kurosaki et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2019)

Review Biochemistry & Molecular Biology

NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis

Katarzyna Skowronska et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

Article Neurosciences

Striatal GluN2B involved in motor skill learning and stimulus-response learning

Yanhong Duan et al.

NEUROPHARMACOLOGY (2018)

Article Cell & Tissue Engineering

Disruption of GRIN2B Impairs Differentiation in Human Neurons

Scott Bell et al.

STEM CELL REPORTS (2018)

Review Biochemistry & Molecular Biology

Flux-Independent NMDAR Signaling: Molecular Mediators, Cellular Functions, and Complexities

Pavel Montes de Oca Balderas

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

Article Neurosciences

Unconventional NMDA Receptor Signaling

Kim Dore et al.

JOURNAL OF NEUROSCIENCE (2017)

Review Biochemistry & Molecular Biology

Mechanisms regulating dendritic arbor patterning

Fernanda Ledda et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2017)

Article Genetics & Heredity

Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains

Sharon A. Swanger et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2016)

Review Pharmacology & Pharmacy

Human GRIN2B variants in neurodevelopmental disorders

Chun Hu et al.

JOURNAL OF PHARMACOLOGICAL SCIENCES (2016)

Article Multidisciplinary Sciences

Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population

Yuto Takasaki et al.

SCIENTIFIC REPORTS (2016)

Article Multidisciplinary Sciences

Association of genetic variants of GRIN2B with autism

Yongcheng Pan et al.

SCIENTIFIC REPORTS (2015)

Review Biochemistry & Molecular Biology

On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors

Karlie N. Fedder et al.

BIOMOLECULES (2015)

Article Clinical Neurology

GRIN2B Mutations in West Syndrome and Intellectual Disability with Focal Epilepsy

Johannes R. Lemke et al.

ANNALS OF NEUROLOGY (2014)

Article Biochemistry & Molecular Biology

Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders

E. M. Kenny et al.

MOLECULAR PSYCHIATRY (2014)

Article Multidisciplinary Sciences

Synaptic, transcriptional and chromatin genes disrupted in autism

Silvia De Rubeis et al.

NATURE (2014)

Article Multidisciplinary Sciences

The contribution of de novo coding mutations to autism spectrum disorder

Ivan Iossifov et al.

NATURE (2014)

Review Neurosciences

ER to synapse trafficking of NMDA receptors

Martin Horak et al.

FRONTIERS IN CELLULAR NEUROSCIENCE (2014)

Article Multidisciplinary Sciences

Recurrent de novo mutations implicate novel genes underlying simplex autism risk

B. J. O'Roak et al.

NATURE COMMUNICATIONS (2014)

Article Clinical Neurology

GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine

Tyler Mark Pierson et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2014)

Review Neurosciences

Influence of GluN2 subunit identity on NMDA receptor function

D. J. A. Wyllie et al.

NEUROPHARMACOLOGY (2013)

Review Clinical Neurology

Diversity in NMDA Receptor Composition: Many Regulators, Many Consequences

Antonio Sanz-Clemente et al.

NEUROSCIENTIST (2013)

Article Genetics & Heredity

Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes

Slave Petrovski et al.

PLOS GENETICS (2013)

Article Biochemistry & Molecular Biology

Glutamate Binding to the GluN2B Subunit Controls Surface Trafficking of N-Methyl-D-aspartate (NMDA) Receptors

Kevin She et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Multidisciplinary Sciences

De novo mutations revealed by whole-exome sequencing are strongly associated with autism

Stephan J. Sanders et al.

NATURE (2012)

Article Neurosciences

Family based association of GRIN2A and GRIN2B with Korean autism spectrum disorders

Hee Jeong Yoo et al.

NEUROSCIENCE LETTERS (2012)

Article Multidisciplinary Sciences

GluN2B subunit deletion reveals key role in acute and chronic ethanol sensitivity of glutamate synapses in bed nucleus of the stria terminalis

Tiffany A. Wills et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

Article Biochemistry & Molecular Biology

Identification of a MicroRNA that Activates Gene Expression by Repressing Nonsense-Mediated RNA Decay

Ivone G. Bruno et al.

MOLECULAR CELL (2011)

Article Genetics & Heredity

Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations

Brian J. O'Roak et al.

NATURE GENETICS (2011)

Article Neurosciences

Dual Palmitoylation of NR2 Subunits Regulates NMDA Receptor Trafficking

Takashi Hayashi et al.

NEURON (2009)

Review Cell Biology

Communication Between the Synapse and the Nucleus in Neuronal Development, Plasticity, and Disease

Sonia Cohen et al.

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY (2008)

Article Neurosciences

Roles of NR2A and NR2B in the development of dendritic arbor morphology in vivo

Rebecca C. Ewald et al.

JOURNAL OF NEUROSCIENCE (2008)

Article Neurosciences

Rapid bidirectional switching of synaptic NMDA receptors

Camilla Bellone et al.

NEURON (2007)

Article Neurosciences

Glutamate exocytosis from astrocytes controls synaptic strength

Pascal Jourdain et al.

NATURE NEUROSCIENCE (2007)