Topic: excitotoxicity

Mitochondrial calcium uniporter (MCU) is a protein that facilitates calcium ion influx into mitochondria. It is well established that MCU, through mitochondrial Ca2+ overload, may promote neuronal death in different neuropathological conditions, especially those involving excitotoxicity. Surprisingly, MCU distribution in hippocampus is inversely proportional to susceptibility of individual hippocampal subregions to death – the highest MCU expression is found in CA2, the lowest - in CA1 (the most and the least resistant regions, respectively). The aim of my study was therefore to assess cell ty

Background: Nowadays, Alzheimer's Disease is the type of dementia with the highest incidence worldwide. NMDA receptor is one of the key players in this pathology, causing neurotoxicity and neuronal death after excessive stimulation. On the other hand, the cannabinoid receptor CB1 induces a neuroprotective role. In this research we aim to analyze the capacity of the CB1R to regulate and reduce NMDAR overstimulation in Alzheimer's pathology.Results: It has been demonstrated that CB1R and NMDAR colocalize and form heteromeric complexes in transfected HEK-293T cells. In the same cells, NMDAR activ

Despite extensive research, effective treatment for Alzheimer’s disease (AD) remains elusive. Emerging evidence suggests that the endocannabinoid system and glutamatergic neurotransmission play important roles in AD pathophysiology. This project aims to elucidate the involvement of cannabinoid type 1 receptor (CB1R) on regulating the cytotoxic effects induced by N-methyl-D-aspartate receptors (NMDARs) in AD. On the one hand, CB1R activation reduces neuroinflammation and promotes neuroprotection in AD models. On the other hand, the synaptic receptor NR2A contribute to synaptic integrity and mem

Excitotoxicity is a central mechanism in the pathogenesis of different, currently incurable, neurodegenerative diseases. One treatment targeting excitotoxicity is Riluzole (Rilutek®), a drug capable of reducing glutamate release. Currently, Riluzole is available for patients with amyotrophic lateral sclerosis (ALS) to delay the progression of the disease. However, its efficacy diminishes in advanced stages of the pathology.The aim of this study has been to characterize the effect of a novel Riluzole-derived compound (VA945) as a potential neuroprotective drug, aiming at identify a more efficie

Astrocytes exhibit dynamic behavior in multiple sclerosis (MS), assuming both pro-inflammatory and anti-inflammatory phenotypes, yet their precise role in modelling the neuroinflammatory response in MS remains elusive. While mice are commonly employed for MS research, murine astrocytes fail to fully replicate the structural and functional complexity of their human counterparts, limiting the translation of findings from in vitro studies to the human context. Leveraging the unique characteristics of patient-derived iPSC astrocytes, this study aims to establish a platform for in vitro exploration

We have developed a novel way to block TRPM4 channel by applying specific antibodies that bind to an extracellular region close to the channel pore. The TRPM4 antibodies include a polyclonal antibody M4P that is specific to rodent TRPM4, a monoclonal antibody M4M that is specific to human TRPM4, and most recently, a humanized antibody M4H modified from M4M.The inhibitory effect of TRPM4 antibodies is achieved via two pathways: 1) directly blocking channel activity; 2) downregulating the surface expression of TRPM4. Under disease condition such as hypoxia/ischemia, blocking TRPM4 activity by ou

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1G93A mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 (layer 2/3) of SOD1G93A mice, throughout disease progression. Astrocytic metabolism was selectively reduced using fluorocitrate (FC). Synaptic plasticity/transmi