LSA Fellows 18 

Project titel: Statin-induced implications on Piezo1-mediated mechanosignaling in the murine central nervous system Projectleader: Dr. Anke Müller

Even the brain, as one of the softest tissues in the body, is exposed to mechanical forces. Besides trauma, inflammatory processes and protein aggregates in the process of neurodegenerative diseases as well as changes of extracellular matrix composition and cytoskeletal rearrangements within cells will produce mechanical forces that contribute to cellular adaptations. Also statins, a widely prescribed drug to treat dyslipidemia, change cholesterol synthesis in the brain and thereby affect cell membrane properties but it remains to be investigated how long-term treatments with statin will affect mechanosignaling. One of the mechanosensitive channels that open upon enhanced membrane tension is Piezo1 and we identified Piezo1 both in rat cortical cultures and in rat brain synaptic terminals but the functional role of this channel in central nervous system neurons is unclear. This project aims to understand how Piezo1-mediated signaling acts on cells and how this will be influenced by statin-induced changes of membrane properties in vitro. As Piezo1 activation modulates cellular processes such as protein synthesis and seems to be involved in regulation of synaptic density, we will look into Piezo1 mediated translational effects and see how statin treatment will influence this process and we will also try to elucidate whether Piezo1 mediates statin-induced changes in synaptic density. As statins are thought to be beneficial in Alzheimer’s disease, we will analyze Piezo1 signaling in an in vitro Alzheimer’s disease model during long-term statin treatment. These insights into statin influences on Piezo1-mediated signaling will contribute to our knowledge about effects by statin treatment and might help to apply this drug in the most beneficial way.