somatostatin modulates insulin-degrading-enzyme metabolism implications for the regulation of microglia activity in ad生长激素抑制素调节insulin-degrading-enzyme代谢影响小胶质细胞活动的规定.pdfVIP

Somatostatin Modulates Insulin-Degrading-Enzyme Metabolism: Implications for the Regulation of Microglia Activity in AD 1 1 1,2 3 3 Grazia Tundo , Chiara Ciaccio , Diego Sbardella , Mariaserena Boraso , Barbara Viviani , 1,2 1 Massimiliano Coletta , Stefano Marini * 1 Department of Experimental Medicine and Biochemical Sciences, University of Roma Tor Vergata, Roma, Italy, 2 Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Bari, Italy, 3 Department of Pharmacological Sciences, University of Milan, Milan, Italy Abstract The deposition of b-amyloid (Ab) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer’s disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Ab, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Ab catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Ab accumulation by partially restoring IDE activity. Citation: Tundo G, Ciaccio C, Sbardella D, Boraso M, Viviani B, et al. (2012) Somatostatin Modulates Insulin-Degrading-Enzyme Metabolism: Implications for the