Conophylline protects cells in cellular models of neurodegenerative diseases by inducing Mammalian target of rapamycin (mTOR)-independent autophagy

Yukiko Sasazawa, Natsumi Sato, Kazuo Umezawa, Siro Simizu

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Macroautophagy is a cellular response that leads to the bulk, nonspecific degradation of cytosolic components, including organelles. In recent years, it has been recognized that autophagy is essential for prevention of neurodegenerative diseases, including Parkinson disease (PD) and Huntington disease (HD). Here, we show that conophylline (CNP), a vinca alkaloid, induces autophagy in an mammalian target of rapamycin-independent manner. Using a cellular model of PD, CNP suppressed protein aggregation and protected cells from cell death caused by treatment with 1-methyl-4-phenylpyridinium, a neurotoxin, by inducing autophagy. Moreover, in the HD model, CNP also eliminated mutant huntingtin aggregates. Our findings demonstrate the possible use of CNP as a therapeutic drug for neurodegenerative disorders, including PD and HD.

Original languageEnglish
Pages (from-to)6168-6178
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number10
DOIs
Publication statusPublished - 2015 Mar 6

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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