Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease

Figure 4

The involvement of zinc metalloproteinases in A𝛽 metabolism. A range of ADAMs (10, 17, 9, 8, 19, and 33) have been implicated in the nonamyloidogenic processing of APP to generate sAPP𝛼 and C83, although the evidence for the latter four enzymes having a direct physiological role in this respect is limited. ADAMs 9 and 15 are capable of cleaving ADAM10 and may be indirectly involved in the activation of the nonamyloidogenic pathway in this respect. Nardilysin also indirectly activates nonamyloidogenic processing of APP via an activation of ADAMs 9, 10, and 17. IDE, NEP, ECE-1, ECE-2, MMPs, GCPII and, possibly, ACE are involved directly in the degradation of A𝛽, and a potential role for catalytically active ADAMs in the degradation of A𝛽 remains to be elucidated.