Anno2016
AutoriPasquale Picone, Silvia Vilasi, Fabio Librizzi, Marco Contardi, Domenico Nuzzo, Luca Caruana, Sara Baldassano, Antonella Amato, Flavia Mulè, Pier Luigi San Biagio, Daniela Giacomazza, Marta Di Carlo
AbstractThe onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic
drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is
delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of ?-
secretase (BACE1) and ?-amyloid precursor protein (APP), promoting processing and aggregation of ?-amyloid (A?), mainly in
the cortex region. Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and
conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and
hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including A?. By using biophysical techniques
we found that metformin is able to directly interact with A? influencing its aggregation kinetics and features. These findings
indicate that metformin induces different adverse effects, leading to an overall increase of the risk of AD onset.
RivistaAging (albany, N.y. Online)
ISSN1945-4589
Impact factor
Volume8
Pagina inizio1718
Pagina fine1734
Autori IBFPier Luigi SAN BIAGIO, Daniela GIACOMAZZA, Silvia VILASI, Fabio LIBRIZZI
Linee di Ricerca IBFMD.P01.002.001
Sedi IBFIBF.PA