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 journalArticle

Abstract

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
Volume116
Issue number4
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Synucleins
Unfolded Protein Response
Parkinsonian Disorders
Theoretical Models
Proteins
Endoplasmic Reticulum
Parkinson Disease
Activating Transcription Factor 4
Brain
Protein Unfolding
Endoplasmic Reticulum Stress
Bearings (structural)
Dopaminergic Neurons
Chemical activation
Brain Diseases
Substantia Nigra
Neurons

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Bellucci, A., Navarria, L., Zaltieri, M., Falarti, E., Bodei, S., Sigala, S., ... Spano, P. (2011). Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease. Journal of Neurochemistry, 116(4), 588-605. https://doi.org/10.1111/j.1471-4159.2010.07143.x

Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease. / Bellucci, Arianna; Navarria, Laura; Zaltieri, Michela; Falarti, Elisa; Bodei, Serena; Sigala, Sandra; Battistin, Leontino; Spillantini, Mariagrazia; Missale, Cristina; Spano, Pierfranco.

In: Journal of Neurochemistry, Vol. 116, No. 4, 02.2011, p. 588-605.

Research output: Contribution to journalArticle

Bellucci, A, Navarria, L, Zaltieri, M, Falarti, E, Bodei, S, Sigala, S, Battistin, L, Spillantini, M, Missale, C & Spano, P 2011, 'Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease', Journal of Neurochemistry, vol. 116, no. 4, pp. 588-605. https://doi.org/10.1111/j.1471-4159.2010.07143.x
Bellucci, Arianna ; Navarria, Laura ; Zaltieri, Michela ; Falarti, Elisa ; Bodei, Serena ; Sigala, Sandra ; Battistin, Leontino ; Spillantini, Mariagrazia ; Missale, Cristina ; Spano, Pierfranco. / Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease. In: Journal of Neurochemistry. 2011 ; Vol. 116, No. 4. pp. 588-605.
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