Regulation of the α-secretase ADAM10 at transcriptional, translational and post-translational levels

A tremendous gain of interest in the biology of ADAM10 emerged during the past 15 years when it has first been shown that this protease was able to target the α-site of the β-amyloid precursor protein (βAPP) and later confirmed as the main physiological α-secretase activity. However, beside its well-established implication in the so-called non-amyloidogenic processing of βAPP and its probable protective role against Alzheimer's disease (AD), this metalloprotease also cleaves many other substrates, thereby being implicated in various physiological as well as pathological processes such as cancer and inflammation. Thus, in view of possible effective therapeutic interventions, a full comprehension of how ADAM10 is up and down regulated is required. This review discusses our current knowledge concerning the implication of this enzyme in AD as well as its more recently established roles in other brain disorders and provides a detailed up-date on its various transcriptional, translational and post-translational modulations.