The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by α-synuclein or amyloid-β (1-42) peptide

Diego Albani, Letizia Polito, Sara Batelli, Stefania De Mauro, Claudia Fracasso, Giuliana Martelli, Laura Colombo, Claudia Manzoni, Mario Salmona, Silvio Caccia, Alessandro Negro, Gianluigi Forloni

Research output: Contribution to journalArticle

Abstract

Human sirtuins are a family of seven conserved proteins (SIRT1-7). The most investigated is the silent mating type information regulation-2 homolog (SIRT1,), which was associated with neuroprotection in models of polyglutamine toxicity or Alzheimer's disease (AD) and whose activation by the phytocompound resveratrol (RES) has been described. We have examined the neuroprotective role of RES in a cellular model of oxidative stress, a common feature of neurodegeneration. RES prevented toxicity triggered by hydrogen peroxide or 6-hydroxydopamine (6-OHDA). This action was likely mediated by SIRT1 activation, as the protection was lost in the presence of the SIRT1 inhibitor sirtinol and when SIRT1 expression was down-regulated by siRNA approach. RES was also able to protect SK-N-BE from the toxicity arising from two aggregation-prone proteins, the AD-involved amyloid-β (1-42) peptide (Aβ42) and the familiar Parkinson's disease linked α-synuclein(A30P) [α-syn(A30P)]. Alpha-syn(A30P) toxicity was restored by sirtinol addition, while a partial RES protective effect against Aβ42 was found even in presence of sirtinol, thus suggesting a direct RES effect on Aβ42 fibrils. We conclude that SIRT1 activation by RES can prevent in our neuroblastoma model the deleterious effects triggered by oxidative stress or α-syn(A30P) aggregation, while RES displayed a SIRT1-independent protective action against Aβ42.

Original languageEnglish
Pages (from-to)1445-1456
Number of pages12
JournalJournal of Neurochemistry
Volume110
Issue number5
DOIs
Publication statusPublished - Sep 2009

Keywords

  • Alpha-synuclein
  • Amyloid-β-protein
  • Autophagy
  • Oxidative stress
  • Resveratrol
  • SIRT1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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