High Throughput Screening of LINGO Ligands: A New Drug Discovery Tool for the Treatment of Neurodegenerative Diseases

FIST SA - 10/27/2016


The invention relates to a screening method of Lingo’s inhibitors using the monitoring of conformational changes of Lingo-1, 2, 3 or 4 induced by the binding of potential ligands. This technology uses bioluminescence resonance energy transfer (BRET) technology and can be performed on living cells, membranes or cellular extracts in microplates. The BRETs induced by potential ligands are measured on a microplate reader and the assay has been applied to high throughput methods.


Actually, there is no simple method allowing the identification of ligands and antagonists of Lingo proteins. This BRET-based assay allows the screening of large libraries in order to identify new potential therapeutic compounds


Lingo-1 is a transmembrane protein preferentially expressed in the central nervous system (CNS) and most specifically in neurons and oligodendrocytes. It has been shown to negatively regulate different processes: (i) the growth of neurite and axons, (ii) the survival of different neurons, (iii) the differentiation of oligodendrocytes and myelinisation. In vitro and in vivo experiments have demonstrated that the inhibition of Lingo-1 is a promising and innovative approach to treat neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, and chronic glaucoma

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