Molecular pathomechanisms of HSPB1 and HSPB8 mutations in motor neuropathies: study of protein-protein interactions and axonal transport in cellular and animal models.

In recent years more than 30 disease-associated genes for inherited peripheral neuropathies have been identified and at least one third of these encode proteins with housekeeping functions, such as: stress response, RNA processing, translation synthesis, and apoptosis (Timmerman et al., 2006). The motor neurons seem to be particularly vulnerable to defects in these housekeeping proteins likely because their large axons have high metabolic requirements for maintenance, transport over long distances and precise connectivity (Van Den Bosch and Timmerman, 2006). In this 4-year project, we will determine how mutations in small HSPs (HSPB1 and HSPB8) contribute to cellular stress in motor neurons by the development and use of cellular and mouse models. By a proteomics approach, we will identify differentially interacting proteins for the mutant and wildtype (wt) HSPB1 and HSPB8. These proteins will provide new insights into the pathomechanisms of motor neuropathies and deliver novel disease associated genes.

Keywords:CELL BIOLOGY, PATHOGENESIS, MOLECULAR GENETICS

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing

Project type:Collaboration project