New protease inhibitors against Alzheimer's disease

Patients with Alzheimer's disease accumulate amyloid-β protein (Aβ) in their brain and it has been suggested that blocking the production of Aβ may interrupt the causality chain of the disease. In the May issue of Nature Cell Biology Agnès Petit and colleagues from the Institut de Pharmacologie Moleculaire et Cellulaire in Nice, and Trophos Inc., Marseille, describe new synthetic drugs that specifically target the production of Aβ without any obvious side effects.

Petit et al designed and tested three new non-peptidic inhibitors of γ-secretase — the enzyme that cleaves the Aβ protein from its βAPP precursor protein. In human cells they show that these inhibitors markedly reduce the production of Aβ and increase the carboxy-terminal fragments of βAPP (Nat Cell Biol 2001, 3:507-511). The compounds did not affect the endoproteolysis of presenilins — proteins that are also a substrate for γ-secretase.

The process of mΔEnotch-1 or endoproteolysis of presenilins is ...