ADAM10 stands for A Disintegrin and Metalloproteinase 10. This membrane protein is a sheddase and thought to be the physiological α-secretase for the amyloid precursor protein (APP). In contrast to cleavage by β-secretase, ADAM10-mediated processing of APP is not amyloidogenic because cleavage takes place within the Aβ region, precluding Aβ generation. The proteolytic processing of APP by ADAM10 produces a secreted ectodomain fragment (sAPPα) that has neuroprotective and neurotrophic properties. For these reasons, increasing ADAM10 activity is viewed as potentially therapeutic for Alzheimer’s disease; however, pharmacological approaches have not yet succeeded.
Besides APP, physiological substrates of ADAM10 include Notch and various immune and growth factor proteins, and the protease itself can be processed into signaling molecules. ADAM10 influences neural development, neuroprotection, and synaptic physiology. Two rare mutations in ADAM10 have been associated with familial late-onset AD.
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