EURON and THEME joint PhD meeting

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EURON and THEME joint meeting 2011
Cathepsin D, a lysosomal aspartyl protease, is used to assess lysosomal
degradation. However, the ratio of active Cathepsin D/pre-pro Cathepsin D was
not change in cells expressing PS1 variants.
Beclin 1 is an essential component in the PI3K class III complex to regulate
autophagic induction. It associates with bcl-2 – an antiapoptotic protein to inhibit
autophagosome build-up under normal nutrient condition. Phosphorylation of
either beclin 1 or bcl-2 results in dissociation of this complex and the activation
of autophagy. Western blotting demonstrates that beclin 1 and bcl-2 levels do
not change upon PS1 variants. Interestingly, phosphorylation of bcl-2 (Ser 70)
significantly increases in PS1wt expressing cells as compared to PS deficient
cells.
Conclusion
Our data indicate that PS regulates the induction of autophagy in steady-state
and during starvation. PS1wt expressing cells show increases in the size and/
or number of autophagic vacuoles in comparison to PS deficient cells. This
accumulation is associated with phosphorylation of bcl-2 at Ser 70.
The involvement of PS in autophagy could also contribute to degradation of AD
- associated proteins