Biological and biophysics aspects of metformin-induced effects: Cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggregates

Flavia Mule', Sara Baldassano, Antonella Amato, Silvia Vilasi, Domenico Nuzzo, Pasquale Picone, Fabio Librizzi, Luca Caruana, Marco Contardi, Pier Luigi San Biagio, Silvia Vilasi, Daniela Giacomazza, Marta Di Carlo, Domenico Nuzzo, Fabio Librizzi, Marta Di Carlo, Pasquale Picone, Pier Luigi San Biagio

Risultato della ricerca: Article

28 Citazioni (Scopus)

Abstract

The 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 β- secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), 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 Aβ. By using biophysical techniques we found that metformin is able to directly interact with Aβ 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.
Lingua originaleEnglish
pagine (da-a)1718-1734
Numero di pagine17
RivistaAging
Volume8
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

  • Ageing
  • Cell Biology

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    Mule', F., Baldassano, S., Amato, A., Vilasi, S., Nuzzo, D., Picone, P., Librizzi, F., Caruana, L., Contardi, M., San Biagio, P. L., Vilasi, S., Giacomazza, D., Di Carlo, M., Nuzzo, D., Librizzi, F., Di Carlo, M., Picone, P., & San Biagio, P. L. (2016). Biological and biophysics aspects of metformin-induced effects: Cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggregates. Aging, 8, 1718-1734.