Activation of the Unfolded Protein Response in Parkinson's Disease

Biochem Biophys Res Commun. 2007 Mar 16;354(3):707-11. doi: 10.1016/j.bbrc.2007.01.043. Epub 2007 Jan 17.

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 2alpha (peIF2alpha) 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 alpha-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 alpha-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopamine / metabolism
  • Endoplasmic Reticulum / metabolism
  • Eukaryotic Initiation Factor-2 / chemistry*
  • Eukaryotic Initiation Factor-2 / metabolism
  • Humans
  • Immunochemistry
  • Melanins / metabolism*
  • Pancreas / pathology
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Phosphorylation
  • Protein Folding*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Time Factors
  • alpha-Synuclein / metabolism*
  • eIF-2 Kinase / chemistry*
  • eIF-2 Kinase / metabolism

Substances

  • Eukaryotic Initiation Factor-2
  • Melanins
  • alpha-Synuclein
  • neuromelanin
  • PERK kinase
  • eIF-2 Kinase
  • Dopamine