A key characteristic in neurodegenerative disease progression is the accumulation of fibril-rich inclusions in the human brain. These form by stacking of misfolded proteins that are rich in beta-sheet secondary structures, which leads to a loss of function of the native proteins and consequential cellular death. The detailed mechanism of formation and effect of these fibrils is still unknown. However, due to their active spreading, templating and toxic characteristics we strive to better understand these assemblies.
Fibrils
Misfolded proteins stack into fibrilar assemblies
Alpha-Synuclein+-
Alpha-synuclein (aSyn) is one of the main proteins of interest in our lab. Parkinson's disease, Multiple System Atrophy and Dementia with Lewy bodies are a few examples of neurodegenerative disorders that can be group together by the term «Synucleinopathies» - a group of diseases around the pathological effect aSyn. In our lab we focus for one part on the structure determination of these fibrils, from purely recombinant samples to directly patient-related (amplified and purified).
TDP-43+-
TAR DNA-binding Protein 43 (commonly known as TDP-43) is the key pathological protein involved in FTD and ALS and is a secondary pathology in numerous other neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington Diseases.