Constrained β-Hairpins Targeting the EphA4 Ligand Binding Domain.

The activity of the receptor tyrosine kinase EphA4 has been implicated in several pathologies including oncology (gastric and pancreatic cancers) and neurodegenerative diseases (amyotrophic lateral sclerosis and Alzheimer's disease). However, advances in validating EphA4 as a possible drug target have been limited by the lack of suitable pharmacological inhibitors. Recently, we reported on the design of potent EphA4 agonistic agents targeting its ligand binding domain (LBD).

Astrocytic Ephrin-B1 Regulates Oligodendrocyte Development and Myelination.

Astrocytes have been implicated in oligodendrocyte development and myelination, however, the mechanisms by which astrocytes regulate oligodendrocytes remain unclear. Our findings suggest a new mechanism that regulates astrocyte-mediated oligodendrocyte development through ephrin-B1 signaling in astrocytes. Using a mouse model, we examined the role of astrocytic ephrin-B1 signaling in oligodendrocyte development by deleting ephrin-B1 specifically in astrocytes during the postnatal days (P)14-P28 period and used mRNA analysis, immunohistochemistry, and mouse behaviors to study its effects on oligodendrocytes and myelination.

EphB2 Signaling Is Implicated in Astrocyte-Mediated Parvalbumin Inhibitory Synapse Development.

Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch-clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice.

An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis.

Cholesterol is an essential membrane structural component and steroid hormone precursor, and is involved in numerous signaling processes. Astrocytes regulate brain cholesterol homeostasis and they supply cholesterol to the needs of neurons. ATP-binding cassette transporter A1 (ABCA1) is the main cholesterol efflux transporter in astrocytes.

Beneficial effects of sound exposure on auditory cortex development in a mouse model of Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is the most common genetic cause of autism and intellectual disability. Fragile X mental retardation gene (Fmr1) knock-out (KO) mice display core deficits of FXS, including abnormally increased sound-evoked responses, and show a delayed development of parvalbumin (PV) cells. Here, we present the surprising result that sound exposure during early development reduces correlates of auditory hypersensitivity in Fmr1 KO mice.