Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease

Arianna Bellucci, Laura Navarria, Michela Zaltieri, Elisa Falarti, Serena Bodei, Sandra Sigala, Leontino Battistin, Mariagrazia Spillantini, Cristina Missale, Pierfranco Spano

Research output: Contribution to journalArticlepeer-review


Accumulation of misfolded proteins in the endoplasmic reticulum (ER) is the main event leading to the induction of the ER stress-related unfolded protein response (UPR). Recent postmortem evaluation, showing that the UPR pathway is activated in nigral dopaminergic neurons bearing α-synuclein inclusions in the brain of Parkinson's disease (PD) patients, suggests that the activation of the UPR may be induced by the accumulation of α-synuclein. In this study, we show that the misfolded protein-sensor/UPR activator glucose-regulated protein 78/immunoglobulin heavy chain-binding protein was bound to α-synuclein and was increased in 'in vitro' and 'in vivo' models showing aggregated α-synuclein accumulation. Moreover, α-synuclein accumulation induced the expression of the UPR-related activating transcription factor 4/cAMP-responsive element-2. These findings indicate that activation of the UPR pathway in the PD brain is associated with α-synuclein accumulation occurring in part within the ER.

Original languageEnglish
Pages (from-to)588-605
Number of pages18
JournalJournal of Neurochemistry
Issue number4
Publication statusPublished - Feb 2011


  • α-synuclein
  • ATF4/CREB-2
  • cytochrome c
  • GRP78/BiP
  • Parkinson's disease
  • unfolded protein response

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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