Evidence map›Paper›PMID 40742404›Full record

ArticleMolecular neurobiology2025

Araloside A Induces Raf/MEK/ERK-Dependent Autophagy to Mitigate Alzheimer's and Parkinson's Pathology in Cellular and C. elegans Models.

Xue Chen, Xing-Yue Zhou, Cai Lan, Hai-Jun Fu, Zhi-Chao Li, Meng-Yi Chen, Yong-Ping Wen, Lu Yu, Da-Lian Qin, An-Guo Wu and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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

12 authors.

Xue Chen *Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
Xing-Yue Zhou *Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
Cai Lan *Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
Hai-Jun FuSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
Zhi-Chao LiSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
Meng-Yi ChenCollege of Food and Bioengineering, Chengdu University, Chengdu, Sichuan 610106, China.
Yong-Ping WenCollege of Food and Bioengineering, Chengdu University, Chengdu, Sichuan 610106, China.
Lu YuSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
Da-Lian QinSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China.
An-Guo WuSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China. wuanguo@swmu.edu.cn.
Jian-Ming WuSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China. jianmingwu@swmu.edu.cn.
Xiao-Gang ZhouSichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Luzhou, Chengdu 611130, Sichuan, China. zxg@swmu.edu.cn.

Funding

The Department of Science and Technology of Sichuan Province 2024YFHZ0361the National Natural Science Foundation of China 81801398The Open Project Program of State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China SKL-KF202311
6 · The paper itself

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by pathological protein aggregation and oxidative stress, leading to progressive neurodegeneration. Enhancing autophagy, the primary intracellular pathway for clearing misfolded proteins, represents a promising therapeutic strategy. In this study, we identify Araloside A (ARA), a triterpenoid saponin derived from Aralia elata, as a potent autophagy inducer that alleviates AD- and PD-related pathology. In neuronal cell models, ARA promotes autophagosome formation, increases LC3-II and Beclin-1 levels, and decreases P62, indicating enhanced autophagic activity. Mechanistic investigations reveal that ARA directly binds to Raf, MEK, and ERK proteins and activates autophagy in a Raf/MEK/ERK-dependent manner. This activation facilitates the clearance of APP, total Tau, phosphorylated Tau, and α-synuclein, thereby reducing cytotoxicity. Furthermore, in transgenic Caenorhabditis elegans models of AD and PD, ARA treatment alleviates protein aggregation and behavioral deficits via ERK-dependent autophagy. Together, these findings identify ARA as a natural compound that enhances autophagic clearance of neurotoxic aggregates via Raf/MEK/ERK pathway activation, offering promising therapeutic insights for neurodegenerative proteinopathies.

Indexed as

Alzheimer DiseaseAutophagyCaenorhabditis elegansMAP Kinase Signaling SystemOleanolic AcidParkinson Diseaseraf Kinasesalpha-SynucleinAnimalsAnimals, Genetically ModifiedDisease Models, AnimalHumansNeuronsalpha-SynucleinOleanolic Acidraf KinasesAlzheimer’s diseaseAraloside AAutophagyParkinson’s diseasePathological proteinsRaf/MEK/ERK

Identifiers

PMID40742404

What OpenQuestion holds

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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.