Computational Chemistry ePosters

To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton…

Y-Aminobutyric acid type A (GABA-A) receptors are GABA-gated ion channels that are assembled of 5 (out of a set of 19) subunits, with six possible different alpha subunits. These differently assembled subunits lead to receptors with unique pharmacological and physiological properties that also show unique anatomical…

Aim: The intricate development of Parkinson's disease (PD) has posed a significant challenge in finding effective treatments. In the current study, a diaryl pyrrole compound, 1-(2-chlorophenyl)-2-methyl-5-(4-chlorophenyl)-1H-Pyrrole, was designed, synthesized, and tested for possible motor function improvement in…

GABA transporter 3 (GAT3) is mainly located in the astrocytes in the brain, and it’s responsible for regulating brain inhibitory neurotransmission through the reuptake of GABA molecules from the synapse. Alterations in GAT3 levels are related to multiple neurodegenerative and neurological diseases making it a…

Gain-of-function variants in the Na+-regulated K+ channel KCNT1 are associated to severe, drug-resistant forms of epilepsy. Quinidine has been used as a KCNT1 blocker, both in vitro and in vivo, though with conflicting clinical outcomes.To identify novel KCNT1 blockers, in the present work an in-house library of >800…

Purinergic P2X receptors (P2XR) are activated by ATP, with 7 different subunits capable of forming homo- or heterotrimeric channels. Widely expressed in the nervous system, P2XR have been implicated in neurological diseases, such as Alzheimer's disease, where overexpression of P2X2, P2X4 and P2X7 is observed. Despite…

Muscimol is a potent agonist of inhibitory GABAA-receptors, which are a heterogenous family of pentameric complexes. Muscimol is considered to bind to all receptor subtypes at the orthosteric β+/α- interface. In one of our recent publications, we observed that the antipsychotic drugs clozapine (CLZ), loxapine (LOX)…

Neuronal chloride homeostasis is determined by KCC2 and NKCC1 transporters responsible for chloride efflux and influx. KCC2 internalization and increased NKCC1 surface expression leads to a pathological state by accumulation of chloride in neurons. Molecules designed to reduce intra-neuronal chloride levels - by…

Alzheimer's disease (AD) is a complex ailment of uncertain origin. The available treatments, restricted to cholinesterase inhibitors and N-methyl-D-aspartate receptor (NMDAR) antagonists, merely relieve symptoms. Given the ineffectiveness of single-target therapies, a more promising approach involves a rational…

Glioblastoma (GBM) is a cancer of the brain that has a high mortality and morbidity rate. In the current study, we aimed to find potential small molecules (50-1500 Dalton) with antiproliferative effects on the human U-87 GBM cell line using a machine learning (ML) based screening tool. A list of 519 small molecules…

Glioblastoma (GBM) is the most aggressive primary brain tumor in humans, characterized by the presence of stem cells, responsible for drug resistance and recurrence. For this reason, the identification of a new therapeutic target for GBM may be a promising challenge in tumor treatment.Many reports suggest that M2…

Type A γ-aminobutyric acid (GABAA) receptors are pentameric ligand-gated chloride channels and serves as the main drivers of fast inhibitory neurotransmission in the vertebrate nervous system. 1,2 Dysfunction of GABAA receptors is implicated in a range of neurological disorders, including schizophrenia, autism, and…

Mirtazapine (MTZ) is a racemic antidepressant drug, consisting of its S(+) and R(-) - enantiomers in a 50:50 mixture. MTZ has been investigated for its potential in the treatment of Rett syndrome, a neurodevelopmental disorder affecting 1/10.000 young females worldwide. However, the mechanisms of action of MTZ are…

The high prevalence of comorbidities between substance use disorder (SUD) and other psychiatric diseases, including depression, suggests that brain dysfunctions underlying these disorders may share partly overlapping pathophysiological mechanisms. Identification of such common dysfunctions is therefore a key asset to…

GABA type A receptors (GABAARs) are ligand-gated pentameric ion channels found throughout vertebrate and invertebrate nervous systems. Although their structure and function are highly conserved, they can be selectively modulated. Among insect GABA receptors, the Rdl variant has received significant attention, and…

Neuronal Kv7 (KCNQ) voltage-gated potassium channels contribute to various neurophysiological functions (such as hearing, learning, and pain modulation), and, when mutated, cause distinct pathologies (such as hearing loss, epilepsy, and intellectual disability). Cannabidiol (CBD) is a pan-Kv7 modulator, Kv7.2/3…

Chronic pain affects nearly 20% of the Canadian population and is now recognized as a disease by the World Health Organization. Moderate to severe pain is currently treated with opioids which are known to cause various side effects (constipation, nausea, respiratory depression, drowsiness) and strong dependence. A…

Alzheimer's disease is the most prevalent form of dementia in elderly, presenting a significant global public health challenge. Its pathological hallmarks include extracellular amyloid β (Aβ) aggregates or senile plaques, intracellular neurofibrillary tangles, and inflammatory processes. Despite recent therapeutic…