Cannabinoid Receptors and Ligands: Lessons from CNS Disorders and the Quest for Novel Treatment Venues.

The potential use of cannabinoids for therapeutic purposes is at the forefront of cannabinoid research which aims to develop innovative strategies to prevent, manage and treat a broad spectrum of human diseases. This chapter briefly reviews the pivotal role of the endocannabinoid system in modulating the central nervous system and its roles on neurodegenerative diseases and brain disorders. Ligand-induced modulation of cannabinoid 1 and 2 receptors to modulate immune response, decrease neurodegeneration and pain are aspects that are also discussed.

Adhesion G protein-coupled receptor, ELTD1, is a potential therapeutic target for retinoblastoma migration and invasion.

Background: Prognosis for pediatric metastatic Retinoblastoma (Rb) is poor and current therapies are limited by high systemic toxicity rates and insufficient therapeutic efficacy for metastatic Rb. Tumor dissemination to the brain is promoted by the heterogeneous adhesive and invasive properties of Rb cells within the tumor. In this study we evaluate, for the first time, the expression, and roles of the ELTD1 and GPR125 adhesion G protein-coupled receptors (GPCRs) in Rb cell migration, viability and invasion.

Targeting the Platelet-Derived Growth Factor-beta Stimulatory Circuitry to Control Retinoblastoma Seeds.

Purpose: Vitreous seeding remains the primary reason for treatment failure in eyes with retinoblastoma (Rb). Systemic and intra-arterial chemotherapy, each with its own inherent set of complications, have improved salvage rates for eyes with advanced disease, but the location and biology of vitreous seeds present a fundamental challenge in developing treatments with minimal toxicity and risk. The aim of this study was to target the platelet-derived growth factor (PDGF)- PDGF-receptor β (PDGFRβ) signaling pathway and investigate its role in the growth of Rb seeds, apoptotic activity, and invasive potential.

Assessing a Science Graduate School Recruitment Symposium.

Ciencia Puerto Rico, a non-profit organization dedicated to promoting science, research and scientific education among Latinos, organized an educational symposium to provide college science majors the tools, opportunities and advice to pursue graduate degrees and succeed in the STEM disciplines. In this article we share our experiences and lessons learned, for others interested in developing large-scale events to recruit underrepresented minorities to STEM and in evaluating the effectiveness of these efforts.

Imaging of kiss-and-run exocytosis of surface receptors in neuronal cultures.

Transmembrane proteins are continuously shuttled from the endosomal compartment to the neuronal plasma membrane by highly regulated and complex trafficking steps. These events are involved in many homeostatic and physiological processes such as neuronal growth, signaling, learning and memory among others. We have previously shown that endosomal exocytosis of the B2 adrenergic receptor (B2AR) and the GluR1-containing AMPA receptor to the neuronal plasma membrane is mediated by two different types of vesicular fusion.

Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1.

G protein-coupled receptors (GPCRs) are the major transducers of external stimuli and key therapeutic targets in many pathological conditions. When activated by different ligands, one receptor can elicit multiple signalling cascades that are mediated by G proteins or β-arrestin, a process defined as functional selectivity or ligand bias. However, the dynamic mechanisms underlying β-arrestin signalling remain unknown.

Supporting diversity in science through social networking.

In this Community Page, we learn how a scientific community leverages social networking tools to connect a group of dispersed scientific researchers in Ciencia Puerto Rico; this effort fosters innovative research and educational collaborations and changes the way scientists interact with the public.

A novel retinoblastoma therapy from genomic and epigenetic analyses.

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated.

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors.

Targeting the p53 pathway in retinoblastoma with subconjunctival Nutlin-3a.

Retinoblastoma is a rare childhood cancer of the retina that begins in utero and is diagnosed in the first years of life. The goals of retinoblastoma treatment are ocular salvage, vision preservation, and reduction of short- and long-term side effects without risking mortality because of tumor dissemination. To identify better chemotherapeutic combinations for the treatment of retinoblastoma, several groups have developed genetic mouse models and orthotopic xenograft models of human retinoblastoma for preclinical testing.

Synaptic proteins are tonotopically graded in postnatal and adult type I and type II spiral ganglion neurons.

Inherent in the design of the mammalian auditory system is the precision necessary to transduce complex sounds and transmit the resulting electrical signals to higher neural centers. Unique specializations in the organ of Corti are required to make this conversion, such that mechanical and electrical properties of hair cell receptors are tailored to their specific role in signal coding. Electrophysiological and immunocytochemical characterizations have shown that this principle also applies to neurons of the spiral ganglion, as evidenced by distinctly different firing features and synaptic protein distributions of neurons that innervate high- and low-frequency regions of the cochlea.

Reciprocal regulation of presynaptic and postsynaptic proteins in bipolar spiral ganglion neurons by neurotrophins.

A unifying principle of sensory system organization is feature extraction by modality-specific neuronal maps in which arrays of neurons show systematically varied response properties and receptive fields. Only beginning to be understood, however, are the mechanisms by which these graded systems are established. In the peripheral auditory system, we have shown previously that the intrinsic firing features of spiral ganglion neurons are influenced by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3).

Firing patterns of type II spiral ganglion neurons in vitro.

Type I and type II spiral ganglion neurons convey auditory information from the sensory receptors in the cochlea to the CNS. The numerous type I neurons have been extensively characterized, but the small population of type II neurons with their unmyelinated axons are undetectable with most recording methods. Despite the paucity of information about the type II neurons, it is clear that they must have a significant role in sound processing because they innervate the large number of outer hair cells that are critical for maintaining normal responses to stimuli.