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Modulation of lysosomal ion channels by mutated PARK9

Modulation of lysosomal ion channels by mutated PARK9

Ruslan Iljitsch Stanika (ORCID: 0000-0002-7651-3131)
  • Grant DOI 10.55776/TAI6292324
  • Funding program 1000 Ideas
  • Status ongoing
  • Start January 1, 2025
  • End December 31, 2026
  • Funding amount € 167,879
  • Project website
  • E-mail

Disciplines

Biology (100%)

Keywords

    Lysosomal channels, Parkinson's disease, ATP13A2, Calcium channels

Abstract

Lysosomes are cellular organelles that contain a large number of active enzymes. These enzymes can break down and digest the cell`s own substances as well as foreign substances. With this function, lysosomes play a key role everyone, as they ensure that cellular degradation processes run smoothly. A disruption in lysosome function therefore has a direct effect on the protein balance and energy metabolism. PARK9 is a protein that functions as an ATPase in lysosomes and presumably regulates the transport of cations. A mutation in the PARK9 gene leads to a rapidly progressing form of Parkinson`s disease. In this project, experimental expertise (patching of lysosomes) is now being applied in neuronal cells in order to investigate the function of PARK9 for the ion balance of lysosomes. To do this, the cells are first treated with a substance that enlarges the lysosomes slightly. This makes them visible under the microscope. In the next step, a lysosome is dissected out of the cell. To do this, the cell wall is carefully broken open using a patch pipette, a glass electrode with a tip diameter of a few micrometers, and the lysosome is then pressed out. A new patch pipette is then used to attach to the lysosome and, once the lysosome membrane has been successfully connected to the pipette, the ion currents of the lysosomes can be measured. The research project can provide the following new insights: 1.for the first time, lysosomal ion channels in neuronal cells can be characterized. 2.an understanding of the role of individual ion channels in cell degeneration, as observed in Parkinson`s disease, may lead to the identification of new targets for the treatment of neurodegenerative diseases. 3. the research will establish a cellular model that can be used to investigate the effect of new drugs on ion channels for the potential treatment of Parkinson`s disease.

Research institution(s)
  • Karl Landsteiner Priv.-Univ. - 100%

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