title: Regulation of α-secretase ADAM10 expression and activity.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg-University Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany. endres_k@psychiatrie.klinik.uni-mainz.de
authors.forename: Kristina
authors.initials: K
authors.lastname: Endres
authors.forename: Falk
authors.initials: F
authors.lastname: Fahrenholz
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human