Rope-like defects in axons of tau mutants under stress

Mechanical stress in neurodegeneration

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In the course of ageing, our brain is subjected to environmental and metabolic stresses. Consequently, its components accumulate molecular and cellular defects over many decades, a reason why the onset of molecular and cellular neuropathology of many neurodegenerative disorders such as Parkinson’s often occurs years before the first motor symptoms characteristic of that disease appear. Luckily, neurons of the nervous system evolved molecular mechanisms to protect their physiology against oxidative and metabolic stresses. The effect of mechanical stresses on the nervous system, however, is understudied. In our lab, we explore the fundamental mechanism of how mechanical stresses contribute to neurodegeneration exploiting the short-lived worm C. elegans as a genetic model system. We use intra- and extracellular optogenetic stress and strain sensors in combination with single cell force spectroscopy to identify changes in protein and cell mechanics. To increase health span during the normal course of aging, we investigate how prosthetic mechanoprotection of the cytoskeleton can prolong the functionality of the nervous system.