The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

Guo, Zhibao; Su, Yingying; Wang, Yi‐Hui; Wang, Wei; Guo, Dazhi

doi:10.3892/mmr.2016.5501

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…Semiquantitative evaluation of ADAM10 mRNA using ISH analysis revealed only the Pontine nuclei as a brain structure not expressing the protease (Kärkkäinen et al, 2000 ). These findings have been confirmed by a recent investigation that also described positive ISH-stainings for neurons of the cerebral cortex, hippocampus, thalamus, and cerebellar granular cells in the CNS of adult mice (Guo et al, 2016 ).…”

Section: Adam10 - Portrait Of a Biologically Versatile Proteasesupporting

confidence: 59%

Regulation of Alpha-Secretase ADAM10 In vitro and In vivo: Genetic, Epigenetic, and Protein-Based Mechanisms

Endres

Deller

2017

Front. Mol. Neurosci.

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ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons, responsible for cleaving APP in a non-amyloidogenic manner. This cleavage results in the production of a neuroprotective APP-derived fragment, APPs-alpha, and an attenuated production of neurotoxic A-beta peptides. An increase in ADAM10 activity shifts the balance of APP processing toward APPs-alpha and protects the brain from amyloid deposition and disease. Thus, increasing ADAM10 activity has been proposed an attractive target for the treatment of neurodegenerative diseases and it appears to be timely to investigate the physiological mechanisms regulating ADAM10 expression. Therefore, in this article, we will (1) review reports on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or protein interactions, (2) describe conditions, which change ADAM10 expression in vitro and in vivo, (3) report how neuronal ADAM10 expression may be regulated in humans, and (4) discuss how this knowledge on the physiological and pathophysiological regulation of ADAM10 may help to preserve or restore brain function.

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Section: Adam10 - Portrait Of a Biologically Versatile Proteasesupporting

confidence: 59%

Regulation of Alpha-Secretase ADAM10 In vitro and In vivo: Genetic, Epigenetic, and Protein-Based Mechanisms

Endres

Deller

2017

Front. Mol. Neurosci.

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“…Our results suggest that the activity or the levels of these enzymes might be higher in neurons than in other cell types of the brain. This notion is supported by a previous study showing that ADAM10 levels are higher in neurons than in astrocytes (39).…”

Section: Discussionsupporting

confidence: 81%

Neuron-derived Thioredoxin-80: a novel regulator of type-I interferon response in microglia

Goikolea¹,

Roussarie

Gereñu

et al. 2022

Preprint

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Oxidative stress and neuroinflammation play a central role in Alzheimer's Disease (AD) pathogenesis. However, the mechanism by which these processes lead to neurodegeneration is still not fully understood. Thioredoxin-1 (Trx1) is an antioxidant protein that can be cleaved into a peptide known as Thioredoxin-80 (Trx80), which modulates monocyte function in the periphery and shows anti-amyloidogenic properties in the brain. In this study we aimed to further clarify the biological function of this peptide and its regulation in the brain. We show that neurons are the main producers of Trx80 in the brain. Trx80 levels increase in vivo both in normal aging and in young APPNL-G-F mouse model of amyloid pathology. Trx80 levels were increased in neurons in primary culture treated with either rotenone or 27-hydroxycholesterol, what suggests that Trx80 production is stimulated upon oxidative stress. RNA-sequencing followed by differential gene expression analysis revealed that Trx80 induces microglia activation into a phenotype compatible with interferon response microglia. Finally, we determine that the induction of this microglia phenotype by Trx80 is Trem2-dependent. This study identifies Trx80 as a novel neuron-derived signaling mechanism that modulates microglia function under stress conditions. Strategies to regulate Trx80 levels could be beneficial against AD pathology.

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“…NMDAR are nonselective cations channels, highly permeable to calcium ions. Given the fact that ADAM10 is ubiquitously expressed in the central nervous system of adult mice [38,39] and calcium influx is known activator of ADAM10, NMDAR agonist-stimulated increase in calcium concentration may result in enhanced ADAM10 activity, leading to rapid NRG2 shedding. However, the results presented by Vullhorst and Buonanno [37] may suggest that ADAM10 is not the only protease responsible for NRG2 shedding, because inhibition of ADAM10 (and metalloproteases in general) had less profound effect on NRG2 shedding than NMDAR antagonist.…”

Section: Discussionmentioning

confidence: 99%

Proteolytic Processing of Neuregulin 2

Czarnek

Bereta

2019

Mol Neurobiol

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Neuregulin 2 (NRG2) belongs to the EGF family of growth factors. Most of this family members require proteolytic cleavage to liberate their ectodomains capable of binding and activating their cognate ErbB receptors. To date, most of the studies investigating proteolytic processing of neuregulins focused on NRG1, which was shown to undergo ectodomain shedding by several ADAM proteases and BACE1 and the remaining fragment was further cleaved by γ-secretase. Recently, NRG2 attracted more attention due to its role in the neurogenesis and modulation of behaviors associated with psychiatric disorders. In this study, we used genetic engineering methods to identify proteases involved in proteolytic processing of murine NRG2. Using non-neuronal cell lines as well as cultures of primary hippocampal neurons, we demonstrated that the major proteases responsible for releasing NRG2 ectodomain are ADAM10 and BACE2. Co-expression of NRG2 and BACE2 in neurons of certain brain structures including medulla oblongata and cerebellar deep nuclei was confirmed via immunohistochemical staining. The cleavage of NRG2 by ADAM10 or BACE2 generates a C-terminal fragment that serves as a substrate for γ-secretase. We also showed that murine NRG2 is subject to post-translational modifications, substantial glycosylation of its extracellular part, and phosphorylation of the cytoplasmic tail.

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The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

Cited by 10 publications

References 23 publications

Regulation of Alpha-Secretase ADAM10 In vitro and In vivo: Genetic, Epigenetic, and Protein-Based Mechanisms

Regulation of Alpha-Secretase ADAM10 In vitro and In vivo: Genetic, Epigenetic, and Protein-Based Mechanisms

Neuron-derived Thioredoxin-80: a novel regulator of type-I interferon response in microglia

Proteolytic Processing of Neuregulin 2

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