AI Article Synopsis
- The accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which is linked to ER stress.
- Recent studies show that the UPR pathway is activated in dopaminergic neurons with α-synuclein inclusions in Parkinson's disease (PD) brains, indicating that α-synuclein buildup may cause this response.
- This research highlights that the UPR sensor protein binds to α-synuclein, and its accumulation leads to increased expression of UPR-related factors, suggesting a connection between α-synuclein aggregation and UPR activation in the PD context.
Article 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.
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| http://dx.doi.org/10.1111/j.1471-4159.2010.07143.x | DOI Listing |
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