Ginkgolic acid promotes autophagy-dependent clearance of intracellular alpha-synuclein aggregates

In this study, the effect on α-syn aggregate clearance of ginkgolic acid (GA), a natural compound extracted from Ginkgo biloba leaves that inhibits SUMOylation amongst other pathways, was assessed in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Depolarization of SH-SY5Y neuroblastoma cells and rat primary cortical neurons with KCl was used to induce α-syn aggregate formation. Cells pre-treated with either GA or the related compound, anacardic acid, revealed a significant decrease in intracytoplasmic aggregates immunopositive for α-syn and SUMO-1. An increased frequency of autophagosomes was also detected with both compounds. GA post-treatment 24 h after depolarization also significantly diminished α-syn aggregate bearing cells, indicating the clearance of pre-formed aggregates. Autophagy inhibitors blocked GA-dependent clearance of α-syn aggregates, but not increased autophagosome frequency. Western analysis revealed that the reduction in α-syn aggregate frequency obtained with GA pre-treatment was not accompanied by a significant change in the abundance of SUMO conjugates. The current findings show that GA can promote autophagy-dependent clearance of α-syn aggregates and may have potential in disease modifying therapy.
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research

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CONCLUSION: Existing in vitro and in vivo data are promising, and highlight that naturally-occurring autophagy-regulating compounds play an important role for the prevention and treatment of neurodegenerative disorders. PMID: 31914904 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
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Source: Applied Biochemistry and Biotechnology - Category: Biochemistry Authors: Tags: Appl Biochem Biotechnol Source Type: research
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Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Tags: Arch Pharm Res Source Type: research
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Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
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Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
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Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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