Neuregulin-1 (NRG-1) and its susceptibility to schizophrenia: a case–control study and meta-analysis

Loh, Han Chern; Tang, Pek Yee; Tee, Shiau Foon; Chow, Tze Jen; Choong, Chee Yen; Lim, Shen Yang; Yong, Hoi Sen

doi:10.1016/j.psychres.2013.01.022

Cited by 12 publications

(6 citation statements)

References 12 publications

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“…Moreover, SZ-like behaviors were reported in mice with reduced expression of NMDAR (Belforte et al, 2010), and in persons taking non-competitive NMDAR antagonists like phencyclidine (PCP) or ketamine (Goebel-Goody et al, 2012a). In line with this, it was found that NRG1, a growth factor that promotes phosphorylation and surface retention of NMDARs was mutated in patients with SZ (Stefansson et al, 2004;Loh et al, 2013). Upon binding to its receptor (ErbB4), NRG1 normally activates Fyn leading to Tyr1472 phosphorylation and surface expression of GluN2B (Bjarnadottir et al, 2007).…”

Section: Schizophreniamentioning

confidence: 86%

“…The level of STEP has been reported to be elevated in AD, the most common neurodegenerative disorder, including in the brain of postmortem AD patients and in several AD mice models like the Tg2576 (Kurup et al, 2010), J20 (Chin et al, 2005), APP/PS1 (Zhang et al, 2013), and 3×Tg-AD mice (Zhang et al, 2010). Dineley et al, 2001;Stevens et al, 2003;Lacor et al, 2004;Chin et al, 2005;Almeida et al, 2006;Venkitaramani et al, 2007Venkitaramani et al, , 2011Tseng et al, 2008;Kurup et al, 2010;Zhang et al, 2010Zhang et al, , 2013Olausson et al, 2012;Xu et al, 2014Xu et al, , 2016Saavedra et al, 2016 Kitada et al, 2009;Chagniel et al, 2014;Kurup et al, 2015;Saavedra et al, 2016;Xu et al, 2016 Desplats et al, 2006;Hodges et al, 2006;Saavedra et al, 2011;Gladding et al, 2012;García-Forn et al, 2018 Stefansson et al, 2004;Barros et al, 2009;Belforte et al, 2010;Carty et al, 2012;Goebel-Goody et al, 2012a;Loh et al, 2013;Xu et al, 2018 Fragile X syndrome…”

Section: Alzheimer's Diseasementioning

confidence: 99%

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The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer’s Disease and Other Neurological Disorders

Mahaman

Huang

Embaye

et al. 2021

Front. Cell Dev. Biol.

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STriatal-Enriched protein tyrosine Phosphatase (STEP) is a tyrosine phosphatase that has been implicated in Alzheimer’s disease (AD), the most common form of dementia, and many other neurological diseases. The protein level and activity of STEP have been found to be elevated in most of these disorders, and specifically in AD as a result of dysregulation of different pathways including PP2B/DARPP32/PP1, PKA as well as impairments of both proteasomal and lysosomal systems. The upregulation in STEP leads to increased binding to, and dephosphorylation of, its substrates which are mainly found to be synaptic plasticity and thus learning and memory related proteins. These proteins include kinases like Fyn, Pyk2, ERK1/2 and both NMDA and AMPA receptor subunits GluN2B and GluA2. The dephosphorylation of these molecules results in inactivation of these kinases and internalization of NMDA and AMPA receptor complexes leading to synapse loss and cognitive impairments. In this study, we aim to review STEP regulation and its implications in AD as well as other neurological disorders and then summarize data on targeting STEP as therapeutic strategy in these diseases.

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Section: Schizophreniamentioning

confidence: 86%

Section: Alzheimer's Diseasementioning

confidence: 99%

The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer’s Disease and Other Neurological Disorders

Mahaman

Huang

Embaye

et al. 2021

Front. Cell Dev. Biol.

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“…Glutamate is a key primary excitatory neurotransmitter that plays a critical role in synaptic plasticity, neuronal toxicity, neuronal development, and signal transduction in the brain ( 9 ), and glutamatergic dysfunction could be involved in the pathogenesis of SZ ( 2 , 10 ). The glutamatergic dysfunction hypothesis, supported by previous and our recent studies that involved glutamate receptor genes, such as GRIN2A ( 11 ), GRIN2B ( 12 ), and NRG1 ( 13 , 14 ), and genes related to glutamatergic transmission, e.g., SCL1A6 ( 3 ) and SLC1A3 ( 15 ). Thus, further exploration of the genes of the glutamate pathway is important for the research of susceptibility genes for SZ.…”

Section: Introductionmentioning

confidence: 59%

Solute Carrier Family 1 (SLC1A1) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population

Chen

et al. 2020

Front. Psychiatry

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Objective Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene ( SLC1A1 ) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results Significant associations were found in genotype and allele frequencies for SNPs rs10815017 ( p = 0.002, 0.030, respectively) and rs2026828 ( p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 ( p = 0.020) and rs7024664 ( p = 0.021) and allele frequency at rs3780412 ( p = 0.026) and rs10974573 ( p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 ( p = 0.015), rs2026828 ( p = 0.011), and rs3780411 ( p = 0.040) in males, and rs7021569 in females ( p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 ( p = 0.003), and rs7021569 ( p = 0.045) in males, and rs10974619 in females ( p = 0.044). However, those associations disappeared after Bonferroni’s correction ( p ’s > 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls ( χ 2 = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ ( p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms.

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“…Our results concur with previous meta-analyses of NRG1 that have reported associations for one or more of these markers (SZGene.org. ), 10 , 30 , 31 , 32 , 33 with the exception of the 3′ SNP rs2954041. To our knowledge, this is the first meta-analysis to identify an association between schizophrenia and rs2954041.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis reveals associations between genetic variation in the 5′ and 3′ regions of Neuregulin-1 and schizophrenia

et al. 2017

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Genetic, post-mortem and neuroimaging studies repeatedly implicate neuregulin-1 (NRG1) as a critical component in the pathophysiology of schizophrenia. Although a number of risk haplotypes along with several genetic polymorphisms in the 5′ and 3′ regions of NRG1 have been linked with schizophrenia, results have been mixed. To reconcile these conflicting findings, we conducted a meta-analysis examining 22 polymorphisms and two haplotypes in NRG1 among 16 720 cases, 20 449 controls and 2157 family trios. We found significant associations for three polymorphisms (rs62510682, rs35753505 and 478B14-848) at the 5′-end and two (rs2954041 and rs10503929) near the 3′-end of NRG1. Population stratification effects were found for the rs35753505 and 478B14-848(4) polymorphisms. There was evidence of heterogeneity for all significant markers and the findings were robust to publication bias. No significant haplotype associations were found. Our results suggest genetic variation at the 5′ and 3′ ends of NRG1 are associated with schizophrenia and provide renewed justification for further investigation of NRG1’s role in the pathophysiology of schizophrenia.

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Neuregulin-1 (NRG-1) and its susceptibility to schizophrenia: a case–control study and meta-analysis

Cited by 12 publications

References 12 publications

The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer’s Disease and Other Neurological Disorders

The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer’s Disease and Other Neurological Disorders

Solute Carrier Family 1 (SLC1A1) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population

Meta-analysis reveals associations between genetic variation in the 5′ and 3′ regions of Neuregulin-1 and schizophrenia

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