Trace Amines and Trace Amine-Associated Receptors: A New Frontier in Cell Signaling

Freyberg, Zachary; Saavedra, Juan M.

doi:10.1007/s10571-020-00800-x

Cited by 13 publications

(13 citation statements)

References 15 publications

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“…It is worth exploring whether and how human SAA1 locally produced in the brain participates in the pathology of AD in the future. In addition, other studies have also reported that SAA is expressed and secreted in glioblastoma (grade IV, most serious astrocytoma) [44] and in the brain after traumatic brain injury [45]. All these findings indicate that the local production of SAA may be related to the pathogenesis of these diseases.…”

Section: Discussionmentioning

confidence: 75%

Serum amyloid A inhibits astrocyte migration via activating p38 MAPK

Lin

Liu

Gong

et al. 2020

J Neuroinflammation

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Background: The accumulation of astrocytes around senile plaques is one of the pathological characteristics in Alzheimer's disease (AD). Serum amyloid A (SAA), known as a major acute-phase protein, colocalizes with senile plaques in AD patients. Here, we demonstrate the role of SAA in astrocyte migration. Methods: The effects of SAA on astrocyte activation and accumulation around amyloid β (Aβ) deposits were detected in APP/PS1 transgenic mice mated with Saa3 −/− mice. SAA expression, astrocyte activation, and colocalization with Aβ deposits were evaluated in mice using immunofluorescence staining and/or Western blotting. The migration of primary cultures of mouse astrocytes and human glioma U251 cells was examined using Boyden chamber assay and scratch-would assay. The actin and microtubule networks, protrusion formation, and Golgi apparatus location in astrocytes were determined using scratch-would assay and immunofluorescence staining. Results: Saa3 expression was significantly induced in aged APP/PS1 transgenic mouse brain. Saa3 deficiency exacerbated astrocyte activation and increased the number of astrocytes around Aβ deposits in APP/PS1 mice. In vitro studies demonstrated that SAA inhibited the migration of primary cultures of astrocytes and U251 cells. Mechanistic studies showed that SAA inhibited astrocyte polarization and protrusion formation via disrupting actin and microtubule reorganization and Golgi reorientation. Inhibition of the p38 MAPK pathway abolished the suppression of SAA on astrocyte migration and polarization. Conclusions: These results suggest that increased SAA in the brain of APP/PS1 mice inhibits the migration of astrocytes to amyloid plaques by activating the p38 MAPK pathway.

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Section: Discussionmentioning

confidence: 75%

Serum amyloid A inhibits astrocyte migration via activating p38 MAPK

Lin

Liu

Gong

et al. 2020

J Neuroinflammation

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“…Moreover, one-carbon metabolic pathways related to fetal programming and epigenetics such as SAM biosynthesis and de novo pyrimidine ribonucleotides biosynthesis [ 70 ] are also predicted targets by the altered miRNAs. In addition, pathways related to the innate (phenylethylamine degradation) and adaptive immune system (T cell activation) were also predicted targets of the GDM-associated circulating miRNAs, suggesting possible moderation of placental immune tolerance by these miRNAs [ 71 ]. Thus, important pathways related to fetal development, epigenetic programming and the immune system could be altered by the miRNAs increased in the maternal circulation in GDM.…”

Section: Discussionmentioning

confidence: 99%

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

Sørensen

Poppel

Desoyé

et al. 2021

Cells

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Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter ‘Vitamin D and lifestyle intervention for GDM prevention (DALI)’ trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.

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“…TAARs belong to a class of G protein-coupled receptors that detect biogenic amines, and only TAAR1 and TAAR4 can be activated by trace amines [ 1 , 2 , 4 , 48 ]. Thus, we examined whether these two receptors participate in the tyramine-induced I A response.…”

Section: Resultsmentioning

confidence: 99%

“…Tyramine, a trace amine derived from the metabolism of amino acids, is naturally found in foods and plants and has been endogenously identified in the mammalian brain and peripheral nervous tissues [ 1 ]. Although several trace amine-associated receptors (TAARs) have been identified, the primary endogenous targets of tyramine are TAAR1 and, to a lesser extent, TAAR4 [ 2 ]. Acting through its receptors, tyramine mediates a variety of important biological effects, such as promoting intracranial hemorrhages, blurry vision, and myocardial injury [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Trace amine-associated receptor 1 regulation of Kv1.4 channels in trigeminal ganglion neurons contributes to nociceptive behaviors

et al. 2023

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Background Trace amines, such as tyramine, are endogenous amino acid metabolites that have been hypothesized to promote headache. However, the underlying cellular and molecular mechanisms remain unknown. Methods Using patch-clamp recording, immunostaining, molecular biological approaches and behaviour tests, we elucidated a critically functional role of tyramine in regulating membrane excitability and pain sensitivity by manipulating Kv1.4 channels in trigeminal ganglion (TG) neurons. Results Application of tyramine to TG neurons decreased the A-type K+ current (IA) in a manner dependent on trace amine-associated receptor 1 (TAAR1). Either siRNA knockdown of Gαo or chemical inhibition of βγ subunit (Gβγ) signaling abrogated the response to tyramine. Antagonism of protein kinase C (PKC) prevented the tyramine-induced IA response, while inhibition of conventional PKC isoforms or protein kinase A elicited no such effect. Tyramine increased the membrane abundance of PKCθ in TG neurons, and either pharmacological or genetic inhibition of PKCθ blocked the TAAR1-mediated IA decrease. Furthermore, PKCθ-dependent IA suppression was mediated by Kv1.4 channels. Knockdown of Kv1.4 abrogated the TAAR1-induced IA decrease, neuronal hyperexcitability, and pain hypersensitivity. In a mouse model of migraine induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus, blockade of TAAR1 signaling attenuated mechanical allodynia; this effect was occluded by lentiviral overexpression of Kv1.4 in TG neurons. Conclusion These results suggest that tyramine induces Kv1.4-mediated IA suppression through stimulation of TAAR1 coupled to the Gβγ-dependent PKCθ signaling cascade, thereby enhancing TG neuronal excitability and mechanical pain sensitivity. Insight into TAAR1 signaling in sensory neurons provides attractive targets for the treatment of headache disorders such as migraine.

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Trace Amines and Trace Amine-Associated Receptors: A New Frontier in Cell Signaling

Cited by 13 publications

References 15 publications

Serum amyloid A inhibits astrocyte migration via activating p38 MAPK

Serum amyloid A inhibits astrocyte migration via activating p38 MAPK

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort

Trace amine-associated receptor 1 regulation of Kv1.4 channels in trigeminal ganglion neurons contributes to nociceptive behaviors

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