| 論文名 |
2-Hydroxypropyl-β-cyclodextrin promotes transcription factor EB-mediated activation of autophagy: implications for therapy. |
| 著者 |
Wensi Song
Fan Wang
Parisa Lotfi
Marco Sardiello
Laura Segatori
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
J Biol Chem. 2014 Apr 4;289(14):10211-22. doi: 10.1074/jbc.M113.506246. Epub 2014 Feb 20. |
| WEBサイト |
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| 論文概要（和文） |
2-ヒドロキシプロピル-β-シクロデキストリンは転写因子EBを介したオートファジーの活性化を促進する：治療への影響 |
| 論文概要（英文） |
2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a Food and Drug Administration-approved excipient used to improve the stability and bioavailability of drugs. Despite its wide use as a drug delivery vehicle and the recent approval of a clinical trial to evaluate its potential for the treatment of a cholesterol storage disorder, the cellular pathways involved in the adaptive response that is activated upon exposure to HPβCD are still poorly defined. Here, we show that cell treatment with HPβCD results in the activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and in enhancement of the cellular autophagic clearance capacity. HPβCD administration promotes transcription factor EB-mediated clearance of proteolipid aggregates that accumulate due to inefficient activity of the lysosome-autophagy system in cells derived from a patient with a lysosomal storage disorder. Interestingly, HPβCD-mediated activation of autophagy was found not to be associated with activation of apoptotic pathways. This study provides a mechanistic understanding of the cellular response to HPβCD treatment, which will inform the development of safe HPβCD-based therapeutic modalities and may enable engineering HPβCD as a platform technology to reduce the accumulation of lysosomal storage material. |
