Mode of action
Neuronal physiology and neurodegeneration depend on the interaction of different cell types and the regulation of molecular pathways. At Neuro-Sys we use pharmacological tools, modulation of gene expression, immunocytochemistry, gene and protein level analysis to carefully dissect the mode of action of your compounds.
CRISPR/Cas9
IN VITRO models
Gene editing with CRISPR/Cas9
Specific genetic mutations have been identified as cause of neurodegenerative diseases or as strong risk factors, in familial or sporadic cases.
At Neuro-Sys, we apply CRISPR/Cas9 technology to modify the genome of human neuronal cell lines to study these disease-related mutations, by homology direct repair for specific point mutations or by non-homologous end joining for constitutive knock out.
These models are proposed for drug screening.
Pharmacological tools
IN VITRO models
We investigate how a neuroactive molecule regulates various pathways such as neurotrophic signalling or protein clearance. We use specific and well-validated antagonists of receptors and inhibitors of enzymes that are highly relevant to neuronal survival, such as:
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NMDA receptors
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TrkB signaling
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NOS/NO/ cGMP pathway
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PI3/Akt signaling
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PPARγ signaling
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ERK signaling
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UPR signaling
siRNA
IN VITRO models
Pharmacological agents interact with receptors or enzymes. They can also modulate, in fine, the expression of genes and proteins. We apply siRNA to invalidate the expression of specific targets to futher characterize the mode of action of test compounds.
IN VITRO models + IN VIVO models
Biomolecular analysis of gene expressions, protein expression/phosphorylation, biochemical essays, will define the mode of action of your compounds:
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Neuroinflammation, via the activation of microglial cells and astrocytes and the release of cytokines.
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Protein clearance via ER stress/UPR signaling and macro-autophagy.
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Cell death pathways (e.g. caspase-dependent apoptosis, necroptosis).
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Mitochondrial pathways and energy metabolism (production of reactive oxygen species, levels of ATP, NADPH).