کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6282191 | 1615133 | 2014 | 6 صفحه PDF | دانلود رایگان |

- Pretreatment with a low dose MG132 enhances aggresome formation.
- Preconditioning of MG132 enhances autophagy turnover under proteasome inhibition.
- Preconditioning stimulus accelerates degradation of protein aggregate.
The abnormal accumulation of protein aggregates is a dominant pathological feature common in neurodegenerative diseases. Autophagy contributes to the processing of aggregated proteins resistant to proteasomal degradation. Autophagic degradation is multi-step process, and especially aggresome formation is a specific and active cellular process for appropriate autophagy-mediated protein homeostasis mechanism. Here, we showed that preconditioning of cells with a non-toxic low dose of MG132 induced autophagy, using an in vitro experimental model that closely represents the characteristics of the autophagy pathway under proteasome inhibition. Clear and large aggresome-like protein accumulation was observed in the perinuclear region of differentiated SH-SY5Y cells with preconditioning stimulus. This results in up-regulation of autophagosome formation and turnover and degradation of intracellular ubiquitinated and p62-bound protein aggregates. Pretreatment with low dose of MG132 attenuated proteinopathy-related cytotoxicity. Together, our experimental model could provide a proper in vitro system for studying the autophagy-related pathophysiology of neurodegeneration, especially therapeutic targeting of intracellular aggresome-like aggregates formation.
Journal: Neuroscience Letters - Volume 566, 30 April 2014, Pages 263-268