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Neurosci Lett. 2014 Apr 30;566:263-8. doi: 10.1016/j.neulet.2014.02.056. Epub 2014 Mar 3.

Preconditioning stimulus of proteasome inhibitor enhances aggresome formation and autophagy in differentiated SH-SY5Y cells.

Author information

1
College of Pharmacy, CHA University, Seongnam, Gyeonggi-do, South Korea; College of Pharmacy, Chonnam National University, Gwangju, South Korea.
2
College of Pharmacy, Chonnam National University, Gwangju, South Korea.
3
College of Pharmacy, CHA University, Seongnam, Gyeonggi-do, South Korea. Electronic address: hjchoi3@cha.ac.kr.

Abstract

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.

KEYWORDS:

Aggregates; Aggresome; Autophagy; Neurodegenerative disease; Preconditioning; Proteasome inhibitor

PMID:
24602982
DOI:
10.1016/j.neulet.2014.02.056
[Indexed for MEDLINE]

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