SP2

Principal Investigator: Rüdiger Horstkorte & Astrid Gesper & Kaya Bork (Institute for Physiological Chemistry, MLU Halle-Wittenberg) & Heidi Olzscha (Medical School Hamburg)

Carolin Neu (PhD): The impact of glycosylation and glycation on the generation and uptake of vehicles in aging cells

Linda Kulka (PhD): Acetylation and glycosylation in protein folding and misfolding: Impact on ageing-related diseases

Acetylation and glycosylation are widespread posttranslational modifications (PTMs) involved in diverse cellular processes and can affect the structure of proteins. We have demonstrated that proteins can misfold and form amyloid structures upon inhibition of histone deacetylases (HDACs) in clinically relevant concentrations. Acetylation plays a role in the aetiology of ageing-related proteinopathies such as Alzheimer’s disease, Parkinson’s disease or Huntington’s disease. Furthermore, aggregate formation is fostered by mis-glycosylation of proteins; for instance, mutations in one key enzyme of terminal glycosylation (sialylation) are responsible for the age-dependent GNE (bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosamine kinase) myopathy. We aim to investigate how acetylation and glycosylation influence protein folding and misfolding, in particular proteins involved in ageing-related diseases. We also analyse, how protein shuttling factors can ameliorate protein misfolding and how a different PTM patterns can influence the shuttling process.

Tom Schneider (MD): The influence of glycation on the severity and progression of the GNE associated disease sialuria