, Volume 217, Issue 3-4, pp 343-352
Date: 04 Oct 2011

Regulation of alpha-secretase ADAM10 expression and activity

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The amyloid precursor protein (APP) has a pivotal role in pathogenesis of Alzheimer’s disease (AD) via its beta- and gamma-secretase-derived cleavage products—the A-beta peptides. An alternative processing pathway provided by the alpha-secretase prevents formation of those toxic peptides and gives rise to the neurotrophic and neuroprotective cleavage product APPs-alpha. The molecular identity of the alpha-secretase has been confirmed recently, and there is consistency about ADAM10 being the most relevant and physiological enzyme of this class. It is not clear to what extent a deficiency in the catalytic activity of ADAM10 contributes to AD pathology and whether a decline occurs in aging humans. Nevertheless, ADAM10 has been suggested as a valuable target for prevention and/or for treatment of Alzheimer’s disease. This review focuses on our knowledge about regulation of ADAM10 on different levels of cell physiology, such as transcription and translation, as well as protein–protein interactions and how this especially in the case of transcriptional regulation by retinoic acids might lead to the development of new therapeutic approaches.