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Last update 23 Jan 2025

NRG3

Last update 23 Jan 2025

Basic Info

Synonyms

neuregulin 3, Neuregulin-3, NRG-3

+ [3]

Introduction

Direct ligand for the ERBB4 tyrosine kinase receptor. Binding results in ligand-stimulated tyrosine phosphorylation and activation of the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3 receptors. May be a survival factor for oligodendrocytes.

Drugs associated with NRG3

HG-1199

Target

NRG3

Mechanism

NRG3 modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NRG3

100 Translational Medicine associated with NRG3

0 Patents (Medical) associated with NRG3

221

Literatures (Medical) associated with NRG3

22 Nov 2024·Briefings in Bioinformatics

Genome-wide association neural networks identify genes linked to family history of Alzheimer’s disease

Article

Author: Choudhry, Hani ; Ghose, Upamanyu ; Amin, Najaf ; van Duijn, Cornelia ; Albukhari, Ashwag ; Almansouri, Majid ; Liu, Qiang ; Sproviero, William ; Shi, Liu ; Fernandes, Marco ; Papathanasiou, Angeliki ; Ulm, Brittany S ; Newby, Danielle ; Nevado-Holgado, Alejo ; Zhu, Taiyu ; Winchester, Laura ; Adams, Cassandra

AbstractAugmenting traditional genome-wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce “genome-wide association neural networks (GWANN)” a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzheimer’s disease (AD). In UK Biobank, we defined cases (n = 42 110) as those with AD or family history of AD and sampled an equal number of controls. The data was split into an 80:20 ratio of training and testing samples, and GWANN was trained on the former followed by identifying associated genes using its performance on the latter. Our method identified 18 genes to be associated with family history of AD. APOE, BIN1, SORL1, ADAM10, APH1B, and SPI1 have been identified by previous AD GWAS. Among the 12 new genes, PCDH9, NRG3, ROR1, LINGO2, SMYD3, and LRRC7 have been associated with neurofibrillary tangles or phosphorylated tau in previous studies. Furthermore, there is evidence for differential transcriptomic or proteomic expression between AD and healthy brains for 10 of the 12 new genes. A series of post hoc analyses resulted in a significantly enriched protein–protein interaction network (P-value < 1 × 10−16), and enrichment of relevant disease and biological pathways such as focal adhesion (P-value = 1 × 10−4), extracellular matrix organization (P-value = 1 × 10−4), Hippo signaling (P-value = 7 × 10−4), Alzheimer’s disease (P-value = 3 × 10−4), and impaired cognition (P-value = 4 × 10−3). Applying NNs for GWAS illustrates their potential to complement existing algorithms and methods and enable the discovery of new associations without the need to expand existing cohorts.

01 Nov 2024·Translational Andrology and Urology

Depletion of intrinsic renal macrophages with moderate-to-high expression of CD163, MRC1, PTH2R, PDE4D, and CUBN in regulating podocyte injury in diabetic nephropathy: a single-cell RNA sequencing analysis

Article

Author: Luo, Jiaru ; Zuo, Junling ; Guo, Yaqiong

BackgroundDiabetic nephropathy (DN), a severe complication of diabetes, is characterized by glomerular and tubular damage, which often leads to end-stage renal disease (ESRD). The role of renal macrophages (Mφs), particularly their phenotypic plasticity and function in DN, remains poorly understood. This study investigated the key factors influencing Mφ polarization and their impact on podocyte (PODO) injury in DN.MethodsSingle-nuclear RNA sequencing (snRNA-seq) data from DN and control (CON) kidney samples were analyzed for cell clustering, differential expression, and cell communication. Mφs were identified and categorized based on their gene expression profiles. The proportions and functions of different Mφ phenotypes were compared between DN and CON samples, with a focus on their interaction with PODOs.ResultsA subset of Mφs, characterized by high expression of CD163, MRC1, PTH2R, PDE4D, and CUBN, was significantly depleted in DN as compared to in CON samples. This depletion was associated with the overexpression of AHR and underexpression of IGF1R, inhibiting the differentiation of these protective Mφs. The remaining Mφs in the DN samples exhibited altered functions, particularly in regulating oxidative stress and tight junctions. Their interaction with PODOs through ligands including NRG3 and THBS1 suggested a role in promoting PODO dysfunction and apoptosis and their contribution to the progression of DN.ConclusionsThe depletion of Mφs with a moderate-to-high expression of CD163, MRC1, PTH2R, PDE4D, and CUBN in patients with DN leads to enhanced PODO injury and apoptosis, highlighting a potential therapeutic target for mitigating DN progression. Further research into the mechanisms governing Mφ-PODO interactions could provide insights into novel treatment strategies for DN.

01 Aug 2024·iScience

Genome-wide association reveals a locus in neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain

Article

Author: Mackenzie, Scott C. ; Whalley, Heather C ; Collins, Frances ; Whalley, Heather C. ; Romaniuk, Liana ; Mackenzie, Scott C ; Whitaker, Lucy H R ; Rahmioglu, Nilufer ; Zondervan, Krina T ; Vincent, Katy ; Horne, Andrew W. ; Whitaker, Lucy H.R. ; Horne, Andrew W ; Coxon, Lydia ; Zondervan, Krina T.

Chronic pelvic pain (CPP) in women with no obvious pelvic pathology has few evidence-based treatment options. Our recent multicenter randomized controlled trial (GaPP2) in women with CPP and no obvious pelvic pathology showed that gabapentin did not relieve pain overall and was associated with more side effects than placebo. We conducted an exploratory genome-wide association study using eligible GaPP2 participants aiming to identify genetic variants associated with gabapentin response. One genome-wide significant association with gabapentin analgesic response was identified, rs4442490, an intron variant located in Neuregulin 3 (NRG3) (p = 2·11×10^-8; OR = 18·82 (95% CI 4·86-72·83). Analysis of a large sample of UK Biobank participants demonstrated phenome-wide significant brain imaging features of rs4442490, particularly implicating the orbitofrontal cortex. NRG3 is expressed predominantly in central nervous system tissues and plays a critical role in nervous system development, maintenance, and repair, suggesting a neurobiologically plausible role in gabapentin efficacy and potential for personalized analgesic treatment.

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