Somatostatin Modulates Insulin-Degrading-Enzyme Metabolism: Implications for the Regulation of Microglia Activity in ADReport as inadecuate




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The deposition of β-amyloid Aβ 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 Aβ, 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 Aβ 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 Aβ accumulation by partially restoring IDE activity.



Author: Grazia Tundo, Chiara Ciaccio, Diego Sbardella, Mariaserena Boraso, Barbara Viviani, Massimiliano Coletta, Stefano Marini

Source: http://plos.srce.hr/



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