ADRB2 gene polymorphism and preterm labor

This article discusses issues related to the role of polymorphism of the ADRB2 gene encoding β2-adrenergic receptor in preterm labor and tocolysis. Information is provided on scientific studies related to the search for associations of the carriage of alleles and genotypes of ADRB2 with the preterm labor, as well as with the pharmacological response to tocolytic therapy using β2-adrenergic agonists. The history of the discovery of the relationship of ADRB2 gene polymorphisms with preterm labor is presented in chronological order. As scientific facts emerge, researchers are faced with the question: how can ADRB2 gene polymorphisms affect physiological processes? That is, whether they affect by changing the primary structure of the receptor or by changing the level of expression. Depending on the answer to this question, pharmacogenetics are faced with a further task: what to study - individual polymorphisms or haplotypes?

β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagy

G protein–coupled receptors (GPCRs) have been shown to play integral roles in Alzheimer’s disease pathogenesis. However, it is unclear how diverse GPCRs similarly affect Aβ and tau pathogenesis. GPCRs share a common mechanism of action via the β-arrestin scaffolding signaling complexes, which not only serve to desensitize GPCRs by internalization, but also mediate multiple downstream signaling events. As signaling via the GPCRs, β2-adrenergic receptor (β2AR), and metabotropic glutamate receptor 2 (mGluR2) promotes hyperphosphorylation of tau, we hypothesized that β-arrestin1 represents a point of convergence for such pathogenic activities. Here, we report that β-arrestins are not only essential for β2AR and mGluR2-mediated increase in pathogenic tau but also show that β-arrestin1 levels are increased in brains of Frontotemporal lobar degeneration (FTLD-tau) patients. Increased β-arrestin1 in turn drives the accumulation of pathogenic tau, whereas reduced ARRB1 alleviates tauopathy and rescues impaired synaptic plasticity and cognitive impairments in PS19 mice. Biochemical and cellular studies show that β-arrestin1 drives tauopathy by destabilizing microtubules and impeding p62/SQSTM1 autophagy flux by interfering with p62 body formation, which promotes pathogenic tau accumulation.