Blocking the phosphatidylinositol 3-kinase pathway inhibits neuregulin-1-mediated rescue of neurotoxicity induced by Aβ1–42

Baik, Tai-Kyoung; Kim, Young-Jung; Kang, Se-Mi; Song, Dae-Yong; Min, Sun Seek; Woo, Ran-Sook

doi:10.1111/jphp.12563

Cited by 10 publications

(10 citation statements)

References 54 publications

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“…Esterase was used to cleave the acetoxymethyl group of DCFH-DA, which was oxidized to dichlorofluorescein (DCF) in the presence of reactive oxygen species. Intracellular fluorescence was measured using a spectrofluorometer (VICTOR2, PerkinElmer, USA) at an emission wavelength of 529 nm and an excitation wavelength of 504 nm (Baik et al 2016 ).…”

Section: Methodsmentioning

confidence: 99%

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Neuregulin1 Attenuates H2O2-Induced Reductions in EAAC1 Protein Levels and Reduces H2O2-Induced Oxidative Stress

et al. 2018

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Neuregulin 1 (NRG1) exhibits potent neuroprotective properties. The aim of the present study was to investigate the antioxidative effects and underlying mechanisms of NRG1 against H2O2-induced oxidative stress in primary rat cortical neurons. The expression level of the excitatory amino acid carrier 1 (EAAC1) protein was measured by Western blotting and immunocytochemistry. The levels of lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity, GPx activity, and mitochondrial membrane potential (∆ψm) were determined to examine cell death and the antioxidant properties of NRG1 in primary rat cortical neurons. H2O2 reduced the expression of EAAC1 in a dose-dependent manner. We found that pretreatment with NRG1 attenuated the H2O2-induced reduction in EAAC1 expression. Moreover, NRG1 reduced the cell death and oxidative stress induced by H2O2. In addition, NRG1 attenuated H2O2-induced reductions in antioxidant enzyme activity and ∆ψm. Our data indicate a role for NRG1 in protecting against oxidative stress via the regulation of EAAC1. These observations may provide novel insights into the mechanisms of NRG1 activity during oxidative stress and may reveal new therapeutic targets for regulating the oxidative stress associated with various neurological diseases.

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Section: Methodsmentioning

confidence: 99%

“…The plate was incubated on a shaker for 20 min at room temperature. The absorbance was read at 450 nm using a VICTOR X3 Multilabel plate reader (PerkinElmer, Shelton, USA) (Baik et al 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Neuregulin1 Attenuates H2O2-Induced Reductions in EAAC1 Protein Levels and Reduces H2O2-Induced Oxidative Stress

et al. 2018

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“…NRGs/ErbB-dependent regulation of hippocampal synaptic plasticity in AD animal models has been also reported. Indeed, NRG1 counteracts amyloid β-induced impairment of LTP in the hippocampal CA1 area and dentate gyrus in mouse slices, through a mechanism involving ErbB4 stimulation [114] and downstream PI3K activation [115]. Moreover, the activation of NRGs/ErbB signaling ameliorates LTP deficits, as well as cognitive abnormalities in adult Tg2576 mice, an AD animal model [116,117].…”

Section: Implications Of Nrg/erbb-dependent Regulation Of Synaptic Plmentioning

confidence: 97%

On the Modulatory Roles of Neuregulins/ErbB Signaling on Synaptic Plasticity

Ledonne

Mercuri

2019

IJMS

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Neuregulins (NRGs) are a family of epidermal growth factor-related proteins, acting on tyrosine kinase receptors of the ErbB family. NRGs play an essential role in the development of the nervous system, since they orchestrate vital functions such as cell differentiation, axonal growth, myelination, and synapse formation. They are also crucially involved in the functioning of adult brain, by directly modulating neuronal excitability, neurotransmission, and synaptic plasticity. Here, we provide a review of the literature documenting the roles of NRGs/ErbB signaling in the modulation of synaptic plasticity, focusing on evidence reported in the hippocampus and midbrain dopamine (DA) nuclei. The emerging picture shows multifaceted roles of NRGs/ErbB receptors, which critically modulate different forms of synaptic plasticity (LTP, LTD, and depotentiation) affecting glutamatergic, GABAergic, and DAergic synapses, by various mechanisms. Further, we discuss the relevance of NRGs/ErbB-dependent synaptic plasticity in the control of brain processes, like learning and memory and the known involvement of NRGs/ErbB signaling in the modulation of synaptic plasticity in brain’s pathological conditions. Current evidence points to a central role of NRGs/ErbB receptors in controlling glutamatergic LTP/LTD and GABAergic LTD at hippocampal CA3–CA1 synapses, as well as glutamatergic LTD in midbrain DA neurons, thus supporting that NRGs/ErbB signaling is essential for proper brain functions, cognitive processes, and complex behaviors. This suggests that dysregulated NRGs/ErbB-dependent synaptic plasticity might contribute to mechanisms underlying different neurological and psychiatric disorders.

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“…In addition to the Aβ peptide, other metabolites of amyloid precursor protein (APP) such as the C-terminal fragments of APP (APP-CTs) have been reported to exert cytotoxic effects in neuronal cells (Baik et al, 2016). Ryu et al (2012) investigated whether NRG1 exerts neuroprotective effects against APP-CTs and attempted to determine the underlying neuroprotective mechanisms.…”

Section: Neuregulin 1 and Admentioning

confidence: 99%

Neuregulins in Neurodegenerative Diseases

Lin

Zhao

2021

Front. Aging Neurosci.

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Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), are typically characterized by progressive neuronal loss and neurological dysfunctions in the nervous system, affecting both memory and motor functions. Neuregulins (NRGs) belong to the epidermal growth factor (EGF)-like family of extracellular ligands and they play an important role in the development, maintenance, and repair of both the central nervous system (CNS) and peripheral nervous system (PNS) through the ErbB signaling pathway. They also regulate multiple intercellular signal transduction and participate in a wide range of biological processes, such as differentiation, migration, and myelination. In this review article, we summarized research on the changes and roles of NRGs in neurodegenerative diseases, especially in AD. We elaborated on the structural features of each NRG subtype and roles of NRG/ErbB signaling networks in neurodegenerative diseases. We also discussed the therapeutic potential of NRGs in the symptom remission of neurodegenerative diseases, which may offer hope for advancing related treatment.

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Blocking the phosphatidylinositol 3-kinase pathway inhibits neuregulin-1-mediated rescue of neurotoxicity induced by Aβ1–42

Abstract: Our results demonstrate that NRG1 signalling exerts a neuroprotective effect against Aβ1-42 -induced neurotoxicity via activation of the PI3K/Akt pathway. Furthermore, this suggests that NRG1 has neuroprotective potential for the treatment of AD.

Cited by 10 publications

References 54 publications

Neuregulin1 Attenuates H2O2-Induced Reductions in EAAC1 Protein Levels and Reduces H2O2-Induced Oxidative Stress

Neuregulin1 Attenuates H2O2-Induced Reductions in EAAC1 Protein Levels and Reduces H2O2-Induced Oxidative Stress

On the Modulatory Roles of Neuregulins/ErbB Signaling on Synaptic Plasticity

Neuregulins in Neurodegenerative Diseases

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