Many neurodegenerative disorders are characterized by the accumulation of proteins forming toxic aggregates inside neurons. Certain proteins contain regions with repeated amino acids that can favor the aggregation process. In the cell, the molecular chaperone system maintains a fully operational protein environment by helping proteins reach and retain their final structure, prerequisite for their functionality. However, two chaperones (DNAJB6b and DNAJB8) were recently identified to also prevent protein aggregation and prolong the lifespan in Parkinson´s and Huntington’s disease mouse models, making them interesting potential therapeutic targets.
Our goal is to identify which proteins inside the cell require DNAJB6b and DNAJB8 for proper folding. We will identify the “client” proteins of the two chaperones by using protein mass spectrometry and biochemical methods. The validation of the newly found interactions, together with the determination of a pattern recognized by the chaperones, will allow the potential design of new therapies for the treatment of amyloid-based neurodegenerative diseases.