Title |
Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway
|
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Published in |
Molecular Neurodegeneration, October 2015
|
DOI | 10.1186/s13024-015-0054-3 |
Pubmed ID | |
Authors |
Sung Min Son, Seokjo Kang, Heesun Choi, Inhee Mook-Jung |
Abstract |
Insulin degrading enzyme (IDE) is a major protease of amyloid beta peptide (Aβ), a prominent toxic protein in Alzheimer's disease (AD) pathogenesis. Previous studies suggested that statins promote IDE secretion; however, the underlying mechanism is unknown, as IDE has no signal sequence. In this study, we found that simvastatin (0.2 μM for 12 h) induced the degradation of extracellular Aβ40, which depended on IDE secretion from primary astrocytes. In addition, simvastatin increased IDE secretion from astrocytes in a time- and dose-dependent manner. Moreover, simvastatin-mediated IDE secretion was mediated by an autophagy-based unconventional secretory pathway, and autophagic flux regulated simvastatin-mediated IDE secretion. Finally, simvastatin activated autophagy via the LKB1-AMPK-mTOR signaling pathway in astrocytes. These results demonstrate a novel pathway for statin-mediated IDE secretion from astrocytes. Modulation of this pathway could provide a potential therapeutic target for treatment of Aβ pathology by enhancing extracellular clearance of Aβ. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | 2% |
Korea, Republic of | 1 | 2% |
Unknown | 64 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 14 | 21% |
Student > Master | 10 | 15% |
Researcher | 8 | 12% |
Student > Bachelor | 7 | 11% |
Student > Doctoral Student | 3 | 5% |
Other | 12 | 18% |
Unknown | 12 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 17 | 26% |
Medicine and Dentistry | 9 | 14% |
Biochemistry, Genetics and Molecular Biology | 8 | 12% |
Neuroscience | 8 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 6% |
Other | 4 | 6% |
Unknown | 16 | 24% |