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.
Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD / G. Tundo, C. Ciaccio, D. Sbardella, M. Boraso, B. Viviani, M. Coletta, S. Marini. - In: PLOS ONE. - ISSN 1932-6203. - 7:4(2012), pp. e34376.e34376.1-e34376.e34376.8.
|Titolo:||Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0034376|
|Appare nelle tipologie:||01 - Articolo su periodico|