Neurodegenerative diseases such as frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) or Huntington's disease are associated with selective loss of certain neuron populations and thus show a specific pattern of symptoms. Over the past years especially, disease genes have been successfully identified and been neuropathologically described. In particular, our group has used motoneurons and muscle cells from patient iPS cells to reveal cellular and molecular pathomechanisms for these diseases and to create a compound screening platform.
In the context of the DZNE cooperation group, the main focus will now be on validating the expression of relevant proteins that have been shown to be involved in the pathogenesis of neurodegeneration, in human tissue ("construct validity"). More precisely, proteins or pathway components involved in disease development or molecular therapeutic targets found in mouse models (but also in other models, e.g. Drosophila, C. elegans) are to be analyzed -prior to human studies- with respect to their expression in phylogenetically young parts of the human brain (those affected in ALS and FTD). The Braak collection, which has been established for decades, as well as the human tissue collection of the Institute of Anatomy and Cell Biology provide well-characterized brain tissue for examination. Furthermore, it will be necessary to intensify research efforts under the heading "Neurodegeneration as Synaptopathy" and related implications for new therapeutic approaches. In continuation of the successful work in the virtual Helmholtz Center in Ulm, especially the role of postsynaptic density (PSD) proteins in neurodegenerative diseases will be further investigated.