Comparison of the protein composition of isolated extracellular vesicles from mouse brain and dissociated brain cell culture medium.

Extracellular vesicles (EVs) play a crucial role in intercellular communication. Characterizing EV protein composition is essential to understand EV function(s). Isolating EVs from cell culture medium is a common approach to study EVs, but it remains unclear whether EVs isolated from in vitro conditions accurately reflect physiological conditions of the same source in vivo tissues.

Impact of a pyridazine derivative on tripartite synapse ultrastructure in hippocampus: a three-dimensional analysis.

Introduction: We previously discovered a pyridazine derivative compound series that can improve cognitive functions in mouse models of Alzheimer's disease. One of the advanced compounds from this series, LDN/OSU-0215111-M3, was selected as the preclinical development candidate. This compound activates local protein translation at the perisynaptic astrocytic process (PAP) and enhances synaptic plasticity sequentially.

Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness.

Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms.

Enhancement of tripartite synapses as a potential therapeutic strategy for Alzheimer's disease: a preclinical study in rTg4510 mice.

Background: The lack of effective treatment options for Alzheimer's disease (AD) is of momentous societal concern. Synaptic loss is the hallmark of AD that correlates best with impaired memory and occurs early in the disease process, before the onset of clinical symptoms. We have developed a small-molecule, pyridazine-based series that enhances the structure and function of both the glial processes and the synaptic boutons that form the tripartite synapse.

Pyridazine-derivatives Enhance Structural and Functional Plasticity of Tripartite Synapse Via Activation of Local Translation in Astrocytic Processes.

Excitatory amino acid transporter 2 (EAAT2) is primarily located in perisynaptic astrocytic processes (PAP) where it plays a critical role in synaptic glutamate homeostasis. Dysregulation of EAAT2 at the translational level has been implicated in a myriad of neurological diseases. We previously discovered that pyridazine analogs can activate EAAT2 translation.

Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease.

Glutamate is the predominant excitatory neurotransmitter in the central nervous system. Excitatory amino acid transporter 2 (EAAT2) is primarily responsible for clearance of extracellular glutamate to prevent neuronal excitotoxicity and hyperexcitability. EAAT2 plays a critical role in regulation of synaptic activity and plasticity.