ArticleScientific reports2020
Cilostazol restores autophagy flux in bafilomycin A1-treated, cultured cortical astrocytes through lysosomal reacidification: roles of PKA, zinc and metallothionein 3.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.Autophagy · 2025Article
- Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376DInternational journal of molecular sciences · 2025Article
- Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lysosomal acidification impairment in astrocyte-mediated neuroinflammation.Journal of neuroinflammation · 2025Review
- Hyperammonemia increases the release of pathological extracellular vesicles from monocytes by impairing lysosomal function and autophagy through the TNFα-cAMP-PKA-LC3 pathway.Frontiers in immunology · 2025Article
- Health Benefits of Epigallocatechin Gallate and Forskolin with a Special Emphasis on Glaucoma and Other Retinal Diseases.Medicina (Kaunas, Lithuania) · 2024Review
- The role of glial autophagy in Alzheimer's disease.Molecular psychiatry · 2023Review
- Human neural stem cells restore spatial memory in a transgenic Alzheimer's disease mouse model by an immunomodulating mechanism.Frontiers in aging neuroscience · 2023Article
- Zinc enhances autophagic flux and lysosomal function through transcription factor EB activation and V-ATPase assembly.Frontiers in cellular neuroscience · 2022Article
- Cathepsin D-Managing the Delicate Balance.Pharmaceutics · 2021Review
- Phagocytic Glial Cells in Brain Homeostasis.Cells · 2021Review
- Review
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4 authors at 2 institutions in 1 country.
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Abstract
Cilostazol, a phosphodiesterase 3 inhibitor, reduces the amyloid-beta (Aβ) burden in mouse models of Alzheimer disease by as yet unidentified mechanisms. In the present study, we examined the possibility that cilostazol ameliorates lysosomal dysfunction. Astrocytes treated with bafilomycin A1 (BafA1) exhibited markedly reduced DND-189 and acridine orange (AO) fluorescence, indicating reduced lysosomal acidity. In both cases, BafA1-induced alkalization was reversed by addition of cilostazol, dibutyryl cAMP or forskolin. All three agents significantly increased free zinc levels in lysosomes, and addition of the zinc chelator TPEN abrogated lysosomal reacidification. These treatments did not raise free zinc levels or reverse BafA1-mediated lysosomal alkalization in metallothionein 3 (Mt3)-null astrocytes, indicating that the increases in zinc in astrocytes were derived mainly from Mt3. Lastly, in FITC-Aβ-treated astrocytes, cilostazol reversed lysosomal alkalization, increased cathepsin D activity, and reduced Aβ accumulation in astrocytes. Cilostazol also reduced mHtt aggregate formation in GFP-mHttQ74-expressing astrocytes. Collectively, our results present the novel finding that cAMP/PKA can overcome the v-ATPase blocking effect of BafA1 in a zinc- and Mt3-dependent manner.
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