Aqueous Extract of<i>Paeonia lactiflora</i>and Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3

Chang, Kuo Hsuan; Chen, Wan Ling; Lee, Li Ching; Lin, Chin‐Feng; Kung, Pin-Jui; Lin, Tianquan; Wu, Yi Ci; Wu, Yih Ru; Chen, Yi Chun; Lee-Chen, Guey Jen; Chen, Chiung Mei

doi:10.1155/2013/471659

Cited by 24 publications

(23 citation statements)

References 38 publications

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“…Most recently, studies have focused on the role of PF in protein aggregation diseases such as Parkinson's disease and Alzheimer's disease and in the degradation of aggregation-prone proteins. For example, Chang et al [ 14 ] found that PF significantly prohibited the aggregation of polyQ proteins and upregulated HSF1 and HSP70 chaperones in both 293 ATXN3/Q75-GFP cells and SH-SY5Y ATXN3/Q75-GFP cells. Others have shown that PF protects PC12 cells against MPP+ induced injury by upregulating the autophagic pathway [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Paeoniflorin onα-Synuclein Degradation Pathway

Cai

Zhang

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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Paeoniflorin (PF) is the major active ingredient in the traditional Chinese medicine Radix. It plays a neuroprotective role by regulating autophagy and the ubiquitin-proteasome degradation pathway. In this study, we found PF significantly reduced cell damage caused by MPP+, returning cells to normal state. Cell viability significantly improved after 24 h exposure to RAPA and PF in the MPP+ group (all P < 0.01). CAT and SOD activities were significantly decreased after PF and RAPA treatment, compared with MPP+ (P < 0.001). In addition, MPP+ activated both LC3-II and E1; RAPA increased LC3-II but inhibited E1. PF significantly upregulated both LC3-II (autophagy) and E1 (ubiquitin-proteasome pathway) expression (P < 0.001), promoted degradation of α-synuclein, and reduced cell damage. We show MPP+ enhanced immunofluorescence signal of intracellular α-synuclein and LC3. Fluorescence intensity of α-synuclein decreased after PF treatment. In conclusion, these data show PF reversed the decline of proteasome activity caused by MPP+ and significantly upregulated both autophagy and ubiquitin-proteasome pathways, promoted the degradation of α-synuclein, and reduced cell damage. These findings suggest PF is a potential therapeutic medicine for neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

The Impact of Paeoniflorin onα-Synuclein Degradation Pathway

Cai

Zhang

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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“…Natural compounds were also studied: the aqueous extract of Paeonia lactiflora and its constituents and the aqueous extract of Glycyrrhiza inflata reduced ataxin‐3 aggregation in cellular models (Chang et al . ; Chen et al . ).…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Machado–Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

Matos

Almeida

Nóbrega

2018

Journal of Neurochemistry

103

127

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Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an incurable disorder, widely regarded as the most common form of spinocerebellar ataxia in the world. MJD/SCA3 arises from mutation of the ATXN3 gene, but this simple monogenic cause contrasts with the complexity of the pathogenic mechanisms that are currently admitted to underlie neuronal dysfunction and death. The aberrantly expanded protein product - ataxin-3 - is known to aggregate and generate toxic species that disrupt several cell systems, including autophagy, proteostasis, transcription, mitochondrial function and signalling. Over the years, research into putative therapeutic approaches has often been devoted to the development of strategies that counteract disease at different stages of cellular pathogenesis. Silencing the pathogenic protein, blocking aggregation, inhibiting toxic proteolytic processing and counteracting dysfunctions of the cellular systems affected have yielded promising ameliorating results in studies with cellular and animal models. The current review analyses the available studies dedicated to the investigation of MJD/SCA3 pathogenesis and the exploration of possible therapeutic strategies, focusing primarily on gene therapy and pharmacological approaches rooted on the molecular and cellular mechanisms of disease.

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“…A pcDNA5/FRT/TO-derived fluorescent reporter plasmid with mCherry, ZsYellow1, and AmCyan1 reporters driven by HSF1 (to enhance chaperone expression), heat shock cognate protein (HSPA8, to drive constitutively expressed HSP70), and heat-inducible HSP70 chaperone (HSPA1A, to drive heat-inducible HSP70) promoter fragments, respectively, was cloned as described. 29 The resulting plasmid was used to generate triple fluorescent reporter cells and maintained in accordance with the supplier’s instructions (Invitrogen). GGA, indole, or NC001-8 (100 nM~100 μM) was added to the medium for 24 hours.…”

Section: Methodsmentioning

confidence: 99%

Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

Kung¹,

Tao²,

Hsu³

et al. 2014

DDDT

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In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment.

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Aqueous Extract ofPaeonia lactifloraand Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3

Cited by 24 publications

References 38 publications

The Impact of Paeoniflorin onα-Synuclein Degradation Pathway

The Impact of Paeoniflorin onα-Synuclein Degradation Pathway

Machado–Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

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