Research Group Molecular Neurodegeneration

Molecular Neurodegeneration

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are age-dependent, so far incurable disorders that are becoming increasingly prevalent as life expectancy grows. A unifying pathological feature of these diseases is the deposition of misfolded amyloid-like proteins inside cells and/or in the extracellular matrix. Although it is clear that aggregating proteins cause damage to the brain, the mechanisms of aggregate toxicity remain incompletely understood. Moreover, it is largely unknown how the demise of the vulnerable neuronal cell types affects the functionality of neural circuits.

Our group is interested in understanding the role of toxic protein aggregates in neurodegenerative diseases, as well as cellular defense systems that cope with the aggregates. We investigate the effects of aggregating proteins in primary neuronal cultures and in vivo in mouse models of neurodegenerative diseases. We use cell biological, biochemical and histological methods to characterize the composition of the aggregates and their impact on cellular functions and cell viability. Behavioural tests are employed to uncover disease-related changes in motor and cognitive functions. In addition, we study pathological alterations in neural circuits with the help of chronic in vivo two-photon imaging.

Our current focus is on Huntington’s disease, a devastating hereditary movement disorder caused by a CAG repeat expansion in the Huntingtin gene. Our goal is to identify molecular pathways and neural circuit impairments that play a role in disease progression and could provide targets for new therapeutic approaches.

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