The involvement of cellular prion protein in the autophagy pathway in neuronal cells

Apoptosis and autophagy are main mechanisms of neuronal death involved in prion diseases. Serum deprivation can induce both pathways to cell death in various types of cells. To investigate whether PrPC is involved in autophagy pathway, we analyzed the level of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, by monitoring the conversion from LC3-I into LC3-II in Zürich I Prnp−/− hippocampal neuronal cells. We found that the expression level of LC3-II was increased in Prnp−/− compared to wild-type cells under serum deprivation. In electron microscopy, increased accumulation of autophagosomes in Prnp−/− cells was correlated with the increase in levels of LC3-II. Interestingly, this up-regulated autophagic activity was retarded by the introduction of PrPC into Prnp−/− cells but not by the introduction of PrPC lacking octapeptide repeat region. Thus, the octapeptide repeat region of PrPC may play a pivotal role in the control of autophagy exhibited by PrPC in neuronal cells.