Neuregulin-1/ErbB network: An emerging modulator of nervous system injury and repair

Kataria, Hardeep; Alizadeh, Arsalan; Karimi-Abdolrezaee, Soheila

doi:10.1016/j.pneurobio.2019.101643

Cited by 89 publications

(67 citation statements)

References 347 publications

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“…There are four members of the neuregulin (NRG) gene in mammals from NRG1 to NRG4. The NRG1 gene is a very large gene in humans, and there are six isoforms with various N-terminal regions (type I to type VI), all characterized by the presence of an epidermal growth factor (EGF)-like domain [8][9][10][11][12]. These isoforms are found in various mammalian organs and are present in the human brain.…”

Section: Introductionmentioning

confidence: 99%

CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease

et al. 2020

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Background: The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation. In Alzheimer's disease (AD) brains, NRG1 accumulates in neuritic plaques. It is difficult to determine if NRG1 has beneficial and/or detrimental effects in AD. BACE1 levels are increased in AD brains and cerebrospinal fluid (CSF) and may lead to enhanced NRG1 secretion, but no study has assessed CSF NRG1 levels in AD and mild cognitive impairment (MCI) patients. Methods: This retrospective study included 162 patients suffering from AD dementia (54), MCI with progression to AD dementia (MCI-AD) (27), non-AD MCI (30), non-AD dementias (30), and neurological controls (27). All patients had neurological examinations, brain MRI, and neuropsychological evaluations. After written informed consent and using enzyme-linked immunosorbent assays (ELISAs), CSF samples were evaluated for Aβ1-42, Aβ1-40, total tau (T-tau), phosphorylated tau on threonine 181 (P-tau), BACE1, growth-associated protein 43 (GAP 43), neurogranin (Ng), and NRG1. Results: Levels of NRG1 were significantly increased in the CSF of AD (+ 36%) and MCI-AD (+ 28%) patients compared to neurological controls and also non-AD MCI and non-AD dementias. In addition, in AD and MCI-AD patients, NRG1 levels positively correlated with Aβ1-42 but not with T-tau, P-tau, and BACE1 levels and negatively correlated with MMSE scores. A longitudinal follow-up study of AD patients revealed a trend (p = 0.08) between CSF NRG1 levels and cognitive decline. In the overall population, NRG1 correlated with MMSE and the synaptic biomarkers GAP 43 and neurogranin.

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Section: Introductionmentioning

confidence: 99%

CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease

et al. 2020

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“…Insu cient ErbB signaling in humans is related to the development of some neurodegenerative diseases, such as multiple sclerosis and Alzheimer's Disease [31]. Recently, the crucial role of the Nrg-1/ErbB network in neurodevelopment has also been identi ed [32]. The FOXO family is evolutionarily conserved and a signi cant arbiter of neural cell fate and function in mammals.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Qiaoshao formula for treatment of premature ejaculation

Wang

et al. 2020

Preprint

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Background Qiaoshao (QS) formula, a traditional Chinese medicine (TCM) comprising seven herbs, has been clinically proven to have a favorable treatment effect on premature ejaculation (PE). However, its underlying pharmacological mechanisms in the treatment of PE need to be further clarified. Methods In the present study, a network pharmacology-based strategy was adopted. The active compounds of QS formula were obtained from the Chinese medicine database, and the potential targets of these compounds were collected from the DrugBank database to construct compound-compound targets network. PE-related targets were identified from human disease databases and used to construct the protein-protein interaction (PPI) networks. Compound-disease target PPI network was constructed by merging the PPI network of disease-targets and compound-targets. Cluster and enrichment analyses were performed on the PPI network of disease targets and compound-disease targets. Results Four primary pharmacological network of QS formula were constructed, including the compound-compound targets network, PPI network of PE-related targets and compounds-disease targets, and the QS-PE mechanism network. The module and pathway enrichment analyses revealed that the QS formula had the potential to affect varieties of biological process and pathways, such as nitric oxide biosynthetic process, oxytocin, thyroid hormone, TNF, PI3K-Akt, and the HIF-1 signaling pathway, that play an important role in the pathogenesis of PE. Conclusion This study preliminarily discovered the potential targets and pathways of QS formula in the treatment of PE, which laid a good foundation for further experimental research.

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“…Bace-1 knockout mice showed CNS hypomyelination with thinner myelin sheaths and reduced levels of phosphorylated Akt (p-Akt), but no differences in the total number of OPCs or mature OLs were found [ 39 ]. However, the role of Nrg1 in CNS myelination remains controversial: Nrg1 improves proliferation, survival, and differentiation of OPCs in vitro through ErbB receptors and can promote remyelination in vivo, but its absence has little to no effect on CNS myelination [ 40 , 41 ].…”

Section: Cell Signaling Pathways Involved In Myelinationmentioning

confidence: 99%

R-Ras GTPases Signaling Role in Myelin Neurodegenerative Diseases

Alcover-Sanchez

Garcia-Martin

Cubelos

2020

IJMS

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Myelination is required for fast and efficient synaptic transmission in vertebrates. In the central nervous system, oligodendrocytes are responsible for creating myelin sheaths that isolate and protect axons, even throughout adulthood. However, when myelin is lost, the failure of remyelination mechanisms can cause neurodegenerative myelin-associated pathologies. From oligodendrocyte progenitor cells to mature myelinating oligodendrocytes, myelination is a highly complex process that involves many elements of cellular signaling, yet many of the mechanisms that coordinate it, remain unknown. In this review, we will focus on the three major pathways involved in myelination (PI3K/Akt/mTOR, ERK1/2-MAPK, and Wnt/β-catenin) and recent advances describing the crosstalk elements which help to regulate them. In addition, we will review the tight relation between Ras GTPases and myelination processes and discuss its potential as novel elements of crosstalk between the pathways. A better understanding of the crosstalk elements orchestrating myelination mechanisms is essential to identify new potential targets to mitigate neurodegeneration.

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Neuregulin-1/ErbB network: An emerging modulator of nervous system injury and repair

Cited by 89 publications

References 347 publications

CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease

CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease

Network pharmacology-based strategy to investigate pharmacological mechanisms of Qiaoshao formula for treatment of premature ejaculation

R-Ras GTPases Signaling Role in Myelin Neurodegenerative Diseases

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