Research focus

​The Laboratory of Neurobiology focuses on the mechanisms of acute and chronic axonal and neuronal degeneration and regeneration, aiming to contribute to the development of a therapy for neurodegenerative disorders. This group intensively studies motor neuron disease (amyotrophic lateral sclerosis (ALS) and hereditary motor neuropathy), frontotemporal dementia and stroke as a paradigm of acute neurodegeneration.

Both a familial (autosomal dominant) and a sporadic form of ALS are known to exist. Mutations in several genes are known to cause familial ALS SOD1 mutations, the recently discovered TDP-43 mutations being the most important ones.

The neurobiology laboratory investigates the role of excitotoxicity and calcium metabolism in the pathogenesis of ALS, the significance of VEGF in this disease, and the contribution of non-neuronal cells to its pathogenesis. Furthermore, the genetic contribution to the pathogenesis of ALS is a main topic of study and has prompted the investigation of axonal transport in motor neuron degeneration. In addition, this group has developed a zebrafish model to perform a morpholino-based screen of disease-modifying factors in ALS.

Mutant SOD1 is thought to induce motor neuron degeneration through aberrant protein folding and aggregation. Consequently, the role of heat shock proteins in motor axonal degeneration is being investigated, and particularly that of HSP27, which is upregulated in ALS spinal cord and mutations of which are known to cause a form of distal hereditary motor neuropathy.

Both clinically and pathologically, there is a clear link between ALS and frontotemporal dementia (FTD). Familial forms of FTD can be caused by mutations in tau and progranulin. The group of Wim Robberecht therefore studies the molecular relationship between these two disorders by investigating the biology of tau, progranulin and TDP-43.

Finally, to elucidate the mechanisms underlying axonal regeneration, paradigms of acute neurodegeneration as relevant to stroke and recovery from stroke are a topic of study in this laboratory.

This research is being conducted using in vitro and in vivo models. Both glial and primary motor neuron cultures are studied. Spontaneous, induced and transgenic models for acute and chronic neurodegeneration are used. Genetic and clinical studies are made possible by this group’s link with the Department of Neurology at the University Hospital Leuven.