title: Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Roma Tor Vergata, Roma, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Tundo
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.forename: Diego
authors.initials: D
authors.lastname: Sbardella
authors.forename: Mariaserena
authors.initials: M
authors.lastname: Boraso
authors.forename: Barbara
authors.initials: B
authors.lastname: Viviani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Coletta
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007339:Insulysin / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D013004:Somatostatin; D020780:Matrix Metalloproteinase 9; D007339:Insulysin; D015282:Octreotide