Over the years, we identified a large number of disease causing genes and mutations for Charcot-Marie-Tooth (CMT) neuropathy. Many of these genes encode proteins that are involved in myelination and maintenance of the peripheral nerve. However, also ubiquitously expressed genes with basic tasks in every cell were found to specifically cause peripheral nerve degeneration. Since the identification of a disease-associated gene is only a first step in unravelling the disease mechanism, we wanted to go further and aim to understand the functional consequences of the pathogenic mutations. We chose to focus on ubiquitously expressed genes that our lab identified to be causative for CMT. We aim to unravel the unique properties of these proteins in peripheral nerve biology as well as explore how these properties are affected upon mutation. To this end, we developed cellular (sensory and motor neurons or Schwann cells) and animal model systems. We are not only investigating the impact of disease-causing mutations on the well established functions of these proteins, but additionally try to identify novel and potentially neurospecific pathways in which these proteins might be involved by undertaking large scale approaches. Our ‘gene-driven’ approach is further complemented by a second research line, which aims to identify the role of the innate immune system in neuroprotection and -degeneration. Understanding how this balance is controlled might allow us to fine-tune or even stimulate an inherent neuroprotective response.
www-site: http://www.vib.be/en/research/scientists/Pages/Vincent-Timmerman-Lab.aspx