Breaking down autophagy and the Ubiquitin Proteasome System

Shinae Jung, Yuhyun Chung, Young J. Oh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Autophagy is an evolutionarily conserved catabolic process that is involved in cellular homeostasis and stress responses. Although basal levels of autophagy are essential for cellular homeostasis, dysregulated autophagy is linked to neurodegeneration. Recent studies using genetic or neurotoxin-based models of Parkinson's disease (PD) detect autophagy. We demonstrate that neurotoxins induce autophagy in dopaminergic neuronal cell line and primary cultured neurons. Based on previous reports, including ones from our laboratory, which show that elevated reactive oxygen species (ROS) and cytosolic calcium are implicated in dopaminergic neurodegeneration, we reasoned that these triggers may play critical roles in determining dysregulated autophagy. Similarly, we have demonstrated that ROS-mediated signals play an essential role in 6-hydroxydopamine (6-OHDA)-induced apoptosis, whereas MPP+ causes elevations in cytosolic calcium and calpain activation. By using these experimental models, we specifically address the question as to whether an increase in ROS or cytosolic calcium governs abnormal flux of autophagy as well as the ubiquitin proteasome system (UPS). So far, our data support a notion that ROS and cytosolic calcium act on a distinct flux of autophagy and the UPS. Our data also raise the possibility of interplay between autophagy and other cell death modes (e.g., caspase- or calpain-dependent cell death) during dopaminergic neurodegeneration.

Original languageEnglish
Pages (from-to)S97-S100
JournalParkinsonism and Related Disorders
Volume46
DOIs
Publication statusPublished - 2018 Jan

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Autophagy
Proteasome Endopeptidase Complex
Ubiquitin
Reactive Oxygen Species
Calcium
Calpain
Oxidopamine
Neurotoxins
Homeostasis
Cell Death
Caspases
Parkinson Disease
Theoretical Models
Apoptosis
Neurons
Cell Line

All Science Journal Classification (ASJC) codes

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

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Breaking down autophagy and the Ubiquitin Proteasome System. / Jung, Shinae; Chung, Yuhyun; Oh, Young J.

In: Parkinsonism and Related Disorders, Vol. 46, 01.2018, p. S97-S100.

Research output: Contribution to journalArticle

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