Role of adherens junctions and apical-basal polarity of neural stem/progenitor cells in the pathogenesis of neurodevelopmental disorders: a novel perspective on congenital Zika syndrome.

Radial glial cells (RGCs) are the neural stem/progenitor cells (NSPCs) that give rise to most of neurons and glial cells that constitute the adult central nervous system. A hallmark of RGCs is their polarization along the apical-basal axis. They extend a long basal process that contacts the pial surface and a short apical process to the ventricular surface. Adherens junctions (AJs) are organized as belt-like structures at the most-apical lateral plasma membrane of the apical processes. These junctional complexes anchor RGCs to each other and allow the recruitment of cytoplasmic proteins that act as apical-basal determinants. It has been proposed that disruption of AJs underlies the onset of different neurodevelopmental disorders. In fact, studies performed in different animal models indicate that loss of function of AJs-related proteins in NSPCs can disrupt cell polarity, imbalance proliferation and/or differentiation rates and increase cell death, which, in turn, lead to disruption of the cytoarchitecture of the ventricular zone, protrusion of non-polarized cells into the ventricles, cortical thinning, and ventriculomegaly/hydrocephalus, among other neuropathological findings. Recent Zika virus (ZIKV) outbreaks and the high comorbidity of ZIKV infection with congenital neurodevelopmental defects have led to the World Health Organization to declare a public emergency of international concern. Thus, noteworthy advances have been made in clinical and experimental ZIKV research. This review summarizes the current knowledge regarding the function of AJs in normal and pathological corticogenesis and focuses on the neuropathological and cellular mechanisms involved in congenital ZIKV syndrome, highlighting the potential role of cell-to-cell junctions between NSPCs in the etiopathogenesis of such syndrome.

Possible role of phytoestrogens in breast cancer via GPER-1/GPR30 signaling.

Estrogens generated within endocrine organs and the reproductive system act as ligands for at least three types of estrogen receptors. Estrogen receptors α (ERα) and ß (ERß) belong to the so-called classical family of estrogen receptors, whereas the G protein-coupled receptor GPR30, also known as GPER-1, has been described as a novel estrogen receptor sited in the cell membrane of target cells. Furthermore, these receptors are under stimulation of a family of exogenous estrogens, known as phytoestrogens, which are a diverse group of non-steroidal plant compounds derived from plant food consumed by humans and animals. Because phytoestrogens are omnipresent in our daily diet, they are becoming increasingly important in both human health and disease. Recent evidence indicates that in addition to classical estrogen receptors, phytoestrogens also activate GPER-1 a relevant observation since GPER-1 is involved in several physiopathological disorders and especially in estrogen-dependent diseases such as breast cancer.The first estrogen receptors discovered were the classical ERα and ERß, but from an evolutionary point of view G protein-coupled receptors trace their origins in history to over a billion years ago suggesting that estrogen receptors like GPER-1 may have been the targets of choice for ancient phytoestrogens and/or estrogens.This review provides a comprehensive and systematic literature search on phytoestrogens and its relationship with classical estrogen receptors and GPER-1 including its role in breast cancer, an issue still under discussion.