ArticleMolecular neurodegeneration2015
Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Mechanistic Role of Astrocytic Rac1 Protein in Alzheimer's Disease.Aging and disease · 2025Review
- Mitigating neuroinflammation in cognitive areas: exploring the impact of HMG-CoA reductase inhibitor.The Biochemical journal · 2024Article
- Metabolic Disorder Therapeutics and their Effects on Memory.CNS & neurological disorders drug targets · 2024Review
- The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.International journal of molecular sciences · 2023Review
- Chronic neuronal activation leads to elevated lactate dehydrogenase A through the AMP-activated protein kinase/hypoxia-inducible factor-1α hypoxia pathway.Brain communications · 2023Article
- Ginsenoside ompound K reduces neuronal damage and improves neuronal synaptic dysfunction by targeting Aβ.Frontiers in pharmacology · 2023Article
- IL-6 secretion of CD4Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Glial Cell-Mediated Neuroinflammation in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review.Pharmaceutical research · 2022Review
- Article
- Key brain cell interactions and contributions to the pathogenesis of Alzheimer's disease.Frontiers in cell and developmental biology · 2022Review
- Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression.Frontiers in cell and developmental biology · 2022Review
- Autophagy-Related Pathways in Vesicular Unconventional Protein Secretion.Frontiers in cell and developmental biology · 2022Review
- Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins.Frontiers in cell and developmental biology · 2022Article
- Article
- Review
- Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer's Disease in Mice.Oxidative medicine and cellular longevity · 2021Article
- Emerging risk of environmental factors: insight mechanisms of Alzheimer's diseases.Environmental science and pollution research international · 2020Review
- Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis.Glia · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInsulin 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.
resultsIn 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.
conclusionsThese 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.