Dataset Information

EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of ?-Synuclein.

ABSTRACT: (-)-Epigallocatechin gallate (EGCG), the major component of green tea, has been re-evaluated with ?-synuclein (?S), a pathological constituent of Parkinson's disease, to elaborate its therapeutic value. EGCG has been demonstrated to not only induce the off-pathway 'compact' oligomers of ?S as suggested previously, but also drastically enhance the amyloid fibril formation of ?S. Considering that the EGCG-induced amyloid fibrils could be a product of on-pathway SDS-sensitive 'transient' oligomers, the polyphenol effect on the transient 'active' oligomers (AOs) was investigated. By facilitating the fibril formation and thus eliminating the toxic AOs, EGCG was shown to suppress the membrane disrupting radiating amyloid fibril formation on the surface of liposomal membranes and thus protect the cells which could be readily affected by AOs. Taken together, EGCG has been suggested to exhibit its protective effect against the ?S-mediated cytotoxicity by not only producing the off-pathway 'compact' oligomers, but also facilitating the conversion of 'active' oligomers into amyloid fibrils.

SUBMITTER: Yang JE

PROVIDER: S-EPMC5738379 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of α-Synuclein.

Yang Jee Eun JE Rhoo Kun Yil KY Lee Soonkoo S Lee Jong Tak JT Park Jae Hyung JH Bhak Ghibom G Paik Seung R SR

Scientific reports 20171220 1

(-)-Epigallocatechin gallate (EGCG), the major component of green tea, has been re-evaluated with α-synuclein (αS), a pathological constituent of Parkinson's disease, to elaborate its therapeutic value. EGCG has been demonstrated to not only induce the off-pathway 'compact' oligomers of αS as suggested previously, but also drastically enhance the amyloid fibril formation of αS. Considering that the EGCG-induced amyloid fibrils could be a product of on-pathway SDS-sensitive 'transient' oligomers, ...[more]

PMID: 29263416

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Project description:?-synuclein (aSyn) expression is implicated in neurodegenerative processes, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In animal models of these diseases, axon pathology often precedes cell death, raising the question of whether aSyn has compartment-specific toxic effects that could require early and/or independent therapeutic intervention. The relevance of axonal pathology to degeneration can only be addressed through longitudinal, in vivo monitoring of different neuronal compartments. With current imaging methods, dopaminergic neurons do not readily lend themselves to such a task in any vertebrate system. We therefore expressed human wild-type aSyn in zebrafish peripheral sensory neurons, which project elaborate superficial axons that can be continuously imaged in vivo. Axonal outgrowth was normal in these neurons but, by 2 days post-fertilization (dpf), many aSyn-expressing axons became dystrophic, with focal varicosities or diffuse beading. Approximately 20% of aSyn-expressing cells died by 3 dpf. Time-lapse imaging revealed that focal axonal swelling, but not overt fragmentation, usually preceded cell death. Co-expressing aSyn with a mitochondrial reporter revealed deficits in mitochondrial transport and morphology even when axons appeared overtly normal. The axon-protective protein Wallerian degeneration slow (WldS) delayed axon degeneration but not cell death caused by aSyn. By contrast, the transcriptional coactivator PGC-1?, which has roles in the regulation of mitochondrial biogenesis and reactive-oxygen-species detoxification, abrogated aSyn toxicity in both the axon and the cell body. The rapid onset of axonal pathology in this system, and the relatively moderate degree of cell death, provide a new model for the study of aSyn toxicity and protection. Moreover, the accessibility of peripheral sensory axons will allow effects of aSyn to be studied in different neuronal compartments and might have utility in screening for novel disease-modifying compounds.

Dataset Information

EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of ?-Synuclein.

Publications

EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of α-Synuclein.

Similar Datasets

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