The Korthlab investigates the molecular underpinnings of chronic brain diseases like neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease) and chronic mental illnesses (schizophrenia, recurrent affective disorders). A specific focus is on protein pathology conceived as the consequence of a disruption of protein homeostasis (proteostasis) during cellular malfunction. Proteostasis is embedded in a trajectory of various disease causes from genes to environment.
What is protein pathology? Protein pathology means that the physiological assembly of cellular protein complexes is changed to an unfavorable and maladaptive way, usually going along with protein misassembly or aggregation. Genetic factors are seen as converging to protein pathology by means of unphysiological expression levels (too low, too high) and/or coding mutants leading to unphysiological folding or interactions (Research focus).
Brain disease conditions are conceptualized as the extremes on a continuum starting with physiological protein assembly to protein misassembly: Protein misassembly can either be subtle as in conditions such as normal brain aging and chronic mental illnesses, or dramatic such as in microscopically visible protein deposits featured in the neurodegenerative diseases. Defining brain diseases from the perspective of protein misassembly has the valuable advantage of immediately providing a pharmacological target. Accordingly, it is our ultimate goal to identify novel pharmacotherapies to chronic mental illnesses and neurodegenerative diseases by targeting protein (mis) assembly (Research focus).
Special focus is on the biological definition of schizophrenia. It is our goal to redefine its purely clinical diagnosis currently based solely on clinical interview and self-reporting, by biological markers identifying subsets of biologically discernible diseases (Research focus; YouTube-Video).
The Korthlab uses molecular techniques, including in vitro and in vivo modeling, to investigate human chronic brain diseases primarily by means of focussing on protein pathology or aberrant protein homeostasis (proteostasis).