Mild MPP+ exposure-induced glucose starvation enhances autophagosome synthesis and impairs its degradation

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, mainly characterised by the progressive loss of dopaminergic neurons. MPP + has been widely used as a PD-related neurotoxin, and their reports suggested the several hypotheses for neuronal cell death. However, most of these hypothes...

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Veröffentlicht in:Scientific reports 2017-04, Vol.7 (1), p.46668, Article 46668
Hauptverfasser: Sakamoto, Shuichiro, Miyara, Masatsugu, Sanoh, Seigo, Ohta, Shigeru, Kotake, Yaichiro
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Sprache:eng
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Zusammenfassung:Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, mainly characterised by the progressive loss of dopaminergic neurons. MPP + has been widely used as a PD-related neurotoxin, and their reports suggested the several hypotheses for neuronal cell death. However, most of these hypotheses come from the studies about the acute MPP + exposure. We previously revealed that mild MPP + exposure (10 and 200 μM), which induces gradual cell death, impairs autophagosome degradation at 48 h. In the present study, we further investigated the specific events of mild MPP + exposure and revealed that mild MPP + exposure causes the cell death through glucose starvation, but not acute toxic model (2.5 and 5 mM). At 36 h after mild MPP + exposure, autophagosome synthesis was enhanced owing to glucose starvation and continued to enhance until 48 h, despite impaired autophagosome degradation. Inhibition of autophagosome synthesis reduced mild MPP + -induced cell death. In conclusion, we clarified that glucose starvation-enhanced autophagosome synthesis occurs at an earlier stage than impaired autophagosome degradation and is important in mild MPP + toxicity.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep46668