Ask about this productRelated genes to: GRIA2 antibody
- Gene:
- GRIA2 NIH gene
- Name:
- glutamate ionotropic receptor AMPA type subunit 2
- Previous symbol:
- GLUR2
- Synonyms:
- GluA2, GLURB
- Chromosome:
- 4q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 1992-02-26
- Date modifiied:
- 2016-02-05
Related products to: GRIA2 antibody
Related articles to: GRIA2 antibody
- Neurodegenerative diseases constitute a major public health burden, with neurotoxicity representing a critical pathogenic mechanism underlying Alzheimer's disease and Parkinson's disease. Current therapeutic approaches are primarily symptomatic and fail to prevent disease progression, highlighting the urgent need for neuroprotective agents that can modulate pathological pathways at their source. Natural fungal metabolites have emerged as promising sources of bioactive compounds with potential neuroprotective properties. This study investigates the neuroprotective potential of bioactive compounds derived from the Arctic fungus Pseudogymnoascus australis (P. australis) using an integrated in silico method. From 120 identified compounds, nine were selected based on favorable blood-brain barrier (BBB) permeability and pharmacokinetic profiles using ADMET 3.0 predictions. These included 2-aminohexadecanoic acid (AHA), 11-aminoundecanoic acid (AUA), and seven others, all exhibiting optimal drug-likeness (>0.83) and suitable CNS-targeting properties. Network pharmacology analysis identified 226 overlapping targets between the fungal compounds and neurotoxicity-associated genes. Nine hub genes (Gria1, Gria2, Gria4, Grik1, Grik2, Grin1, Grin2a, Grin2b, and Grin2c) were identified as critical nodes. Enrichment analyses revealed significant involvement in the neuroactive ligand-receptor interaction pathway, suggesting these compounds modulate ionotropic glutamate receptors. Molecular docking analysis showed strong binding affinities, with 78% of ligand-receptor complexes displaying RMSD values below 2.0 Å. AHA and Grik1 emerged as the most promising pair, with a docking score of -7.90 kcal/mol and excellent pharmacokinetic properties (drug-likeness: 0.462, BBB penetration: 0.985). Molecular dynamics simulations over 100 nanoseconds confirmed complex stability, with a mean RMSD of 2.45 Å and binding energies averaging -169.02 kcal/mol, demonstrating sustained ligand-protein interactions. These computational findings provide evidence that P. australis contains bioactive compounds capable of attenuating neurotoxicity through sustained modulation of glutamate receptors, with molecular dynamics validation supporting the thermodynamic stability and potential therapeutic relevance of these interactions. - Source: PubMed
Publication date: 2026/05/17
Naomi RuthAl-Amin MdSmykla JerzyRizman-Idid MohammedChong Teoh TeowMurthy Jaya KumarZubairi Saiful IrwanDavid PamelaSatriawan HerlandBakar Nurlizah AbuAlias Siti Aisyah - Ferroptosis is one of the important mechanisms of secondary neuronal death after spinal cord injury (SCI). However, the upstream regulators that could be targeted for therapeutic intervention remain poorly defined. This study identifies gamma-glutamyl transferase 1 (GGT1) as a key driver of ferroptosis, upregulated in neurons post-SCI. Screening a 150-compound natural product library, we discovered Enocyanin (EA), which reduced GGT1 protein levels, protected neurons from hypoxic injury, and exhibited anti-ferroptotic effects. Mechanistically, EA promoted GGT1 degradation through the E3 ligase MGRN1, leading to K48-linked polyubiquitination and proteasomal clearance, halting ferroptosis. To improve EA's stability and delivery, we engineered a biomimetic nanoplatform (NSCm@EA) using neural stem cell membranes, enhancing drug accumulation at the injured spinal cord. At single-cell resolution, NSCm@EA was shown to precisely remodel neuronal subpopulations, selectively expanding γ-motor neurons and upregulating synaptic genes such as Gria2 and Negr1, while suppressing inflammatory and oxidative stress pathways. In summary, this study reveals GGT1's role in ferroptosis, identifies a natural product that induces its ubiquitin-mediated degradation, and presents a targeted biomimetic delivery strategy for precise intervention in spinal cord injury. - Source: PubMed
Publication date: 2026/05/14
Yang TaoYe LeiXie PeigenSong TaoChen JianZhao HengLiu ZhengshanChen XiDing JianingDing XintianShao AoWu MiaomiaoZhao FengdongTao SiyueYou Tao - Histone deacetylases (HDACs) regulate neuroprotection; however, Trichostatin A (TSA), an HDAC inhibitor, lacks clear molecular mechanisms and core targets in Alzheimer's disease (AD), limiting clinical translation. This study aimed to decipher TSA's AD-regulating network, screen core genes, and support AD early diagnosis and multi-target therapies. - Source: PubMed
Publication date: 2026/04/20
Ou ChangzeChen BinbinDeng JunLong Huajun - Understanding how chromosome 21 gene dosage contributes to neurodevelopmental phenotypes in trisomy 21 (T21) remains a fundamental challenge. Here, we perform transcriptome-wide RNA-sequencing of fetal cortical and hippocampal tissues from T21 cases and euploid controls collected during mid-gestation, a critical window for human brain development. We identify widespread gene expression dysregulation with significant enrichment for chromosome 21 genes and perturbation of neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes is ADARB1, a chromosome 21-encoded RNA editing enzyme, whose overexpression associates with increased adenosine-to-inosine RNA editing, with consistent over-editing at functionally important recoding sites in glutamate and GABA receptor-related genes, including GRIK2, GRIA2, GRIA3, and GABRA3, across cortex and hippocampus. Meta-analyses across independent transcriptomic datasets validate robust chromosome 21 dosage effects, including ADARB1 overexpression and over-editing at 3'UTRs and GRIA3. These findings implicate dysregulated RNA editing as a post-transcriptional mechanism contributing to fetal neuropathology in T21. - Source: PubMed
Publication date: 2026/03/31
Breen Michael SYang AndyWang XuranRodriguez de Los Santos MiguelTao RanWeinberger Daniel RKleinman Joel EMihova KalinaStancheva GerganaSavova SylviaKaneva RadkaDimitrova VioletaVladimirov VladimirHyde Thomas MBuxbaum Joseph D - AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate the fast component of excitatory neurotransmission. They govern synaptic plasticity that underlies learning and memory, while their dysregulation is implicated in numerous neurological disorders. The functional diversity of AMPARs arises from variations in their subunit composition and also their association with auxiliary subunits. While multiple structures of homomeric AMPARs have been reported, structural information for the heteromeric core - particularly in the absence of auxiliary subunits, which would serve as a functional and structural baseline - has been limited. Here, we report cryo-electron microscopy structures of GluA1/A2, the most abundant AMPAR di-heteromer in the brain, in the closed, open, and desensitized states. Using molecular dynamics (MD) simulations and cross-correlating structural and functional information, we find that auxiliary subunits increase the diameter of channel pore, which corresponds to larger conductance. Likewise, we find that recovery from desensitization slows with greater disruption of two-fold rotational symmetry of the ligand-binding domain dimer in the desensitized state. Both receptor activation and desensitization vary with the type and number of associated auxiliary proteins. These structures offer a foundation for uncovering how auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric AMPARs. - Source: PubMed
Publication date: 2026/03/28
Yen Laura YNewton Thomas PYelshanskaya Maria VAktolun MuhammedGangwar Shanti PalClausen Rasmus PKurnikova Maria GSobolevsky Alexander I