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Dihydromyricetin an...
Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy
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- Wu, Jia-Zhen (författare)
- Northeastern University,Sheng Jing Hospital,China Medical University, Shenyang
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- Ardah, Mustafa (författare)
- United Arab Emirates University
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- Haikal, Caroline (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups
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- Svanbergsson, Alexander (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups
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- Diepenbroek, Meike (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups
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- Vaikath, Nishant N (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,Hamad Bin Khalifa University
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- Li, Wen (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups
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- Wang, Zhan-You (författare)
- China Medical University, Shenyang
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- Outeiro, Tiago F (författare)
- University Medical Center Göttingen,Max Planck Institute of Experimental Medicine
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- El-Agnaf, Omar M (författare)
- Hamad Bin Khalifa University
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- Li, Jia-Yi (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,Northeastern University,China Medical University, Shenyang
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(creator_code:org_t)
- 2019-06-15
- 2019
- Engelska.
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Ingår i: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 8
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://translationa...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson's disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation in vitro and in vivo. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity.Results: In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 μM) and Sal B (50 μM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice.Conclusions: Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson's disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Wu, Jia-Zhen
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Ardah, Mustafa
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Haikal, Caroline
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Svanbergsson, Al ...
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Diepenbroek, Mei ...
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Vaikath, Nishant ...
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visa fler...
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Li, Wen
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Wang, Zhan-You
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Outeiro, Tiago F
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El-Agnaf, Omar M
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Li, Jia-Yi
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
- Artiklar i publikationen
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Translational Ne ...
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Lunds universitet