Hanse Lecture Nova - Prof. Dr. Janine Kirstein, University of Bremen

'Protein Origami and Neurodegenerative Diseases'

Huntington´s disease (HD) is a neurodegenerative disease caused by an expansion of a stretch of CAG nucleotides, encoding for the amino acid glutamine within the gene huntingtin. The glutamine expansion renders the mutated protein highly aggregation prone that eventually leads to the formation of long fibrillar structures. Huntingtin’s disease is a late age of onset disease and it is therefore assumed that our cellular protein quality control network can suppress the formation of Huntingtin fibrils at younger age. This shows the potential for therapeutic interference by boosting our protein folding capacity to delay disease onset. We could recently identify a trimeric protein complex composed of three molecular chaperones that can completely suppress and also reverse the formation of Huntingtin fibrils in vitro, and in HD-patient derived neurons. Our lab is interested to uncover the mechanisms of how molecular chaperones can remodel toxic proteins that are associated with neurodegenerative diseases. We use interdisciplinary approaches including cells, nematodes and biochemical methods and bioinformatics. In the upcoming talk I will share with you our recent advances on the identification of a unique binding interface between the chaperones and mutant Huntingtin. These data are of prime interest to understand and highjack molecular chaperones as pharmacological target to combat neurodegenerative diseases.