Activation of the unfolded protein response in Parkinson's disease

J.J.M. Hoozemans, E.S. van Haastert, P. Eikelenboom, R.A.I. de Vos, J.M. Rozemuller, W. Scheper

Research output: Contribution to JournalArticleAcademicpeer-review

353 Citations (Scopus)

Abstract

Parkinson's disease (PD) is, at the neuropathological level, characterized by the accumulation of misfolded proteins. The presence of misfolded proteins can trigger a cellular stress response in the endoplasmic reticulum (ER) called the Unfolded Protein Response (UPR). The UPR has been shown to be involved in cellular models for PD. In this study, we investigated UPR activation in the substantia nigra of control and PD patients. Immunoreactivity for the UPR activation markers phosphorylated pancreatic ER kinase (pPERK) and phosphorylated eukaryotic initiation factor 2α (peIF2α) is detected in neuromelanin containing dopaminergic neurons in the substantia nigra of PD cases but not in control cases. In addition, pPERK immunoreactivity is colocalized with increased α-synuclein immunoreactivity in dopaminergic neurons. These data show that the UPR is activated in PD and that UPR activation is closely associated with the accumulation and aggregation of α-synuclein. © 2007 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)707-711
Number of pages5
JournalBiochemical and biophysical research communications
Volume354
Issue number3
DOIs
Publication statusPublished - 16 Mar 2007

Keywords

  • Dopamine
  • Endoplasmic Reticulum
  • Eukaryotic Initiation Factor-2
  • Humans
  • Immunochemistry
  • Journal Article
  • Melanins
  • Pancreas
  • Parkinson Disease
  • Phosphorylation
  • Protein Folding
  • Research Support, Non-U.S. Gov't
  • Substantia Nigra
  • Time Factors
  • alpha-Synuclein
  • eIF-2 Kinase

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