Evidence map›Paper›PMID 37673867›Full record

ArticleCell death & disease2023

A small molecule 20C from Gastrodia elata inhibits α-synuclein aggregation and prevents progression of Parkinson's disease.

Ye Peng, Jun-Rui Ye, Sha-Sha Wang, Wen-Bin He, Zhong-Ping Feng, Hong-Shuo Sun, Shi-Feng Chu, Zhao Zhang, Nai-Hong Chen

Abstract read
In one paragraph

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ye PengSchool of Pharmacy, Minzu University of China, Beijing, 100081, China.
Jun-Rui YeState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medical & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Sha-Sha WangScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Wen-Bin HeShanxi University of Chinese Medicine, National International Joint Research Center for Molecular Chinese Medicine, Taiyuan, 030024, China.
Zhong-Ping FengDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Hong-Shuo SunDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.ORCID http://orcid.org/0000-0001-5142-1874
Shi-Feng ChuState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medical & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. chushifeng@imm.ac.cn.ORCID http://orcid.org/0000-0002-6406-9846
Zhao ZhangState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medical & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. zhangzhao@imm.ac.cn.ORCID http://orcid.org/0000-0001-5363-2157
Nai-Hong ChenSchool of Pharmacy, Minzu University of China, Beijing, 100081, China. chennh@imm.ac.cn.ORCID http://orcid.org/0000-0001-6354-7853

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Parkinson's disease (PD) is pathologically manifested by the aggregation of α-synuclein, which has been envisioned as a promising disease-modifying target for PD. Here, we identified 20C, a bibenzyl compound derived from Gastrodia elata, able to inhibit the aggregation of A53T variants of α-synuclein directly in vitro. Computational analysis revealed that 20C binds to cavities in mature α-synuclein fibrils, and it indeed displays a strong interaction with α-synuclein and reduced their β-sheet structure by microscale thermophoresis and circular dichroism, respectively. Moreover, incubating neural cells with 20C reduced the amounts of α-synuclein inclusions significantly. The treatment of A53T α-Syn transgenic mice with 20C significantly reduces the toxic α-synuclein levels, improves behavioral performance, rescues dopaminergic neuron, and enhances functional connections between SNc and PD associated brain areas. The transcriptome analysis of SNc demonstrated that 20C improves mitochondrial dynamics, which protects mitochondrial morphology and function against α-synuclein induced degeneration. Overall, 20C appears to be a promising candidate for the treatment of PD.

Indexed as

GastrodiaParkinson Diseasealpha-SynucleinAnimalsBrainDopaminergic NeuronsMiceMice, Transgenicalpha-Synuclein

Identifiers

PMID37673867
PMCPMC10482970

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.