Gamma-secretase is a pivotal enzymatic activity in Alzheimer disease that was hidden within a huge number of unrelated proteases.

A protease complex containing presenilin, nicastrin, PEN-2 and probably APH-1 provides the long sought gamma-secretase activity.

Presenilin itself appears to be a novel polytopic aspartyl protease of the GxGD type, whereas the other components might be required for substrate recognition, complex assembly, stability and targeting of the complex to its sites of action.

References

 Haass C, Steiner H. Alzheimer disease gamma-secretase : a complex story of GxGD-type presenilin proteases. Trends Cell Biol. 2002 Dec ;12(12):556-62. PMID : #12495843#