Related Experiment Video
Updated: Sep 19, 2025

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
Published on: November 25, 2022
Nucleolin inhibits α-synuclein to attenuate aconitine's neurotoxicity
Guangxin Liu1, Wenqiang Zuo2, Zhen Zhang3
1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; Sanhang Institute for Brain Science and Technology, Northwestern Polytechnical University, Xi'an 710129, PR China.
Background:
Aconitine (AC), a toxic alkaloid derived from Aconitum species, presents a significant risk of neurotoxicity with global poisoning reports.
Purpose:
This study aimed to reveal the mechanism underlying the neurotoxicity of AC.
Methods:
The toxicity of AC was evaluated by behavioral tests, histological examinations, western blot (WB) and immunofluorescence. We studied its potential mechanism through transcriptome, proteomics, nascent transcripts and immunoprecipitation/mass spectrometry (IP/MS).
Results:
AC caused motor dysfunction and anxiety-like behaviors. And the peak of pyroptosis occurred at 8 h, accompanied by abnormal neurotransmitter-related metabolite expressions in brain tissue, ultrastructural damage and morphological changes in neurons. Importantly, transcriptomic and proteomic analyses indicate the elevation of α-synuclein (α-syn) level and the activation of the PI3K/Akt/mTOR pathway are key drivers of AC neurotoxicity. IP/MS further elucidated that nucleolin (Ncl) is essential for clearing p-α-syn (Ser129). The nascent transcript discovered that the peaks of nascent mRNA of Snca and Ncl appeared at 8 h after AC exposure. Meanwhile, we verified that AC activates the PI3K/Akt/mTOR pathway. Moreover, the hypothesis that Ncl is involved in reducing neurotoxicity by antagonizing AC - induced elevation of α-syn has been further verified in WB and motor behavior studies.
Conclusion:
Our work reveals that the neurotoxicity induced by AC is attributed to the abnormal elevation of α-syn, and nucleolin has a clearance effect.
More Related Videos
09:36Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
10:03Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
Published on: August 16, 2020
Related Concept Videos
Drugs Affecting Neurotransmitter Synthesis
Drugs Affecting Neurotransmitter Release or Uptake
Neural Regulation
The Nucleolus
ATP Synthase: Mechanism
Neurochemical Transmission: Sites of Drug Action