Protein misfolding & aggregation

Researchers at CIP use a multi-angle approach to investigate mechanisms by which soluble amyloidogenic proteins (including: human lysozyme, alpha-synuclein and polyglutamine proteins) assemble into amyloid fibrils.

Their original approach to identify and characterize these proteins in terms of structure, stability, kinetic of formation and toxicity involves:

  • The generation of heavy-chain antibody fragments (also referred as Nanobodies) specific of the amyloidogenic proteins that can be used (i) as structural probes and (ii) as potential inhibitor of the aggregation process
  • The creation of chimeric proteins composed of the beta-lactamase BlaP and amyloidogenic peptides to investigate the role of the amyloid stretches in the process of aggregation and to generate antibodies against specific amyloidogenic peptides

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

AMPA potentiators

The AMPA subtype of glutamatergic receptors is the main actor in the excitatory neurotransmission in the mammalian central nervous system. These receptors are involved in the expression and the maintenance of the long-term potentiation, a phenomenon closely linked to cognitive and memorization processes.

Based on experimental data collected in recent years, the use of AMPA potentiators seems to be an interesting approach in the treatment of cognitive deficits (e.g. Alzheimer’s disease), schizophrenia or depression. Such AMPA signal potentiation could be mediated by positive allosteric modulators (PAMs) of the AMPA receptors, a class of compounds able to produce a fine signal tuning in the presence of the endogenous ligand in the synapse, providing less toxicity than direct agonists.
With this approach, the University of Liège developed many series of AMPA potentiators, among which 1,2,4-benzothiadiazine 1,1-dioxides (BTDs). The team is currently developing BTDs positive allosteric modulator radiolabeled with a fluorin-18 atom that can potentially be used in a clinical setting. For more information, click here.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Thiamine & neuronal death prevention

Researchers at GIGA have a large expertise in the analysis of thiamine compounds. Few years ago, they have discovered a new thiamine derivative: the adenosine thiamine triphosphate.

Their current research focuses on the use of thiamine and its precursors as therapeutic agents in neurodegenerative diseases due to their high bioavailability. More particularly, they aim at identifying the pharmacologically active thiamine compound and investigating its mechanisms of action.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Diagnostic biomarkers

We are looking for new diagnostic biomarkers of Parkinson’s disease from biological samples. We aimed at developing an induced pluripotent stem cell model of alpha-synuclein overexpression to test diagnostic biomarkers and new disease-modifying therapies of Parkinson’s disease.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Potassium channel modulators

The new compounds based on disubstituted anilines, by opening potassium channels, can be used for the treatment of vasospastic disorders (i.e. subarachnoid hemorrhage and migraine), of various diseases of the central nervous system (i.e. epilepsy, ischemia and neurodegenerative diseases) as well as pain treatment.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Calcium-activated potassium channel modulators

Small conductance calcium-activated potassium (SK, KCa2) channels represent interesting and challenging targets in medicinal chemistry. So far, the reference ligand is apamin, a peptide including the [125I] analog for binding studies. Nonpeptidic ligands with high affinity have been developed for several years. Currently, different questions remain to be solved since no selective and brain-penetrating agent is available. In addition, replacing [125I]apamin in binding experiments would be also interesting.

Researchers at CIRM have developed different series of compounds exhibiting significant affinity for SK channels.

These new compounds may act as SK channels blockers or may interact selectively with one of the three subtypes (i.e. SK1, SK2, SK3) offering a novel approach to the treatment of CNS diseases (i.e. Alzheimer’s disease, Parkinson’s disease, neurodegenerative disorders, psychotic disorders, cognitive dysfunction, alcohol and drug addiction, depression…).

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Novel pharmaceutical formulations

Researchers at ULg have a broad expertise in the development of novel pharmaceutical formulations to improve the solubility and the bioavailability of compounds and to facilitate drug delivery to brain cells.

To test these new formulations, they have also developed a cellular blood brain barrier model using immortalized human cerebral microvascular endothelial cells.

For more information, click here.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

In silico modeling

Researchers at GIGA have developed simple mathematical models to investigate several theories of migration of neuroblasts through the rostral migratory stream proposed in the literature, including chemo-attraction, chemorepulsion, general inhibition and the presence of a migration-inducing protein. Apart from the general inhibition model, all the models were able to provide results in good qualitative correspondence with the experimental observations.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!