Transregional Collaborative Research Centre 152
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P04 - Endolysosomal cation channels in synucleo- and tauopathies

Mutations in lysosomal proteins can result in neurodegenerative lysosomal storage disorders (LSDs). As shown in the last funding period activation of lysosomal two-pore channel 2 (TPC2) ameliorates cellular LSD phenotypes e.g., accumulation of cholesterol, lipofuscin, or abnormal vacuole formation. TPC2 activation, which promotes lysosomal exocytosis and autophagy, was assessed in LSD patient fibroblasts, in neurons derived from human LSD iPSC models, and in-vivo. In the next funding period, we will focus on adult-onset neurodegenerative diseases such as Parkinson’s or Alzheimer’s disease (PD, AD) to test whether activation of TPC2 or its relative TRPML1 can rescue PD/AD phenotypes in iPSC models.

Christian Grimm

Univ.-Prof. Dr. Dr. Christian Grimm

Ludwig-Maximilians-Universität in Munich