Glycogen Synthase Kinase-3β Regulates Cellular Prion Protein Levels
The normal cellular prion protein (PrPC) is an essential substrate in all forms of prion diseases and a receptor for A{beta} oligomers in Alzheimers disease. However, it is not fully understood how cells regulate PrPC levels. Recently, we identified glycogen synthase kinase-3{beta} (GSK-3{beta}) as a potential regulator of PrPC levels in a whole genome knockout screen. Here, we show that both…
Glycogen Synthase Kinase-3β (GSK-3β) plays a pivotal role in determining the levels of the cellular prion protein (PrPC), according to recent research. This discovery was made through a whole genome knockout screen, where GSK-3β was identified as a potential regulator of PrPC levels. The study found that both surface and total PrPC levels can be decreased through siRNA-mediated Gsk3b knockdown or CRISPR-mediated Gs3b knockout.
Additionally, whole cell mass spectrometric analysis revealed that PrPC was the 60th most significantly reduced protein (out of 7227 total proteins) in Gsk3b knockout cells. The findings suggest that GSK-3β exerts its regulatory effect on PrPC levels through a post-translational mechanism. Furthermore, treatments with GSK-3β inhibitors, such as laduviglusib (CHIR-99021) and AZD-1080, as well as cycloheximide treatment, were found to reduce PrPC levels in both undifferentiated and differentiated mouse CAD5 and human BE(2)-C cells.
These results indicate that GSK-3β activity controls PrPC levels in living cells, presenting a novel regulatory mechanism and a promising therapeutic target for related diseases.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
