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Updated: Sep 26, 2025
Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease
Published on: June 23, 2023
7,8-Dihydroxyflavone ameliorates mitochondrial impairment and motor dysfunction in the α-synuclein 1-103 transgenic
Ye Tian1, Lina Pan1, Xin Yuan1
1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Abstract:
Parkinson's disease (PD) is the most common motor-associated neurodegenerative disease. Although the pathogenesis of PD is still wrapped in the mist, accumulating evidence indicates that mitochondrial dysfunction contributes to the onset and progression of PD. We previously reported that the lysosomal protease asparagine endopeptidase (AEP) cleaves α-synuclein in the brains of PD patients. The major product, α-synuclein 1-103, significantly promotes PD-like histological changes and motor dysfunction. However, the underlying molecular mechanisms remain unknown. Here we show that α-synuclein 1-103 fragment interacts with mitochondria and induces morphological and functional abnormalities of mitochondria. Furthermore, we investigated the protective effects of 7,8-dihydroxyflavone (7,8-DHF) on mitochondrial dysfunction induced by α-synuclein 1-103 fragment. We found that 7,8-DHF ameliorated α-synuclein 1-103-induced mitochondrial impairment and motor dysfunction. These results indicate that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating PD.
Insights
A novel Parkinson's disease (PD) fragment, alpha-synuclein 1-103, impairs mitochondria. The compound 7,8-dihydroxyflavone (7,8-DHF) protected against this mitochondrial dysfunction and motor deficits, suggesting its therapeutic potential for PD.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Parkinson's disease (PD) is a common neurodegenerative disorder.
- Mitochondrial dysfunction is implicated in PD pathogenesis.
- Asparagine endopeptidase (AEP) cleaves alpha-synuclein in PD brains, producing a neurotoxic fragment.
Purpose of the Study:
- To elucidate the molecular mechanisms by which the alpha-synuclein 1-103 fragment contributes to PD.
- To investigate the protective effects of 7,8-dihydroxyflavone (7,8-DHF) against alpha-synuclein 1-103-induced mitochondrial damage and motor deficits.
Main Methods:
- Investigated the interaction of alpha-synuclein 1-103 fragment with mitochondria.
- Assessed mitochondrial morphology and function following exposure to the fragment.
- Evaluated the efficacy of 7,8-DHF in ameliorating these pathological changes in a PD model.
Main Results:
- The alpha-synuclein 1-103 fragment was found to interact with mitochondria, causing morphological and functional abnormalities.
- 7,8-DHF treatment significantly improved mitochondrial function and structure.
- 7,8-DHF administration also ameliorated motor dysfunction associated with the alpha-synuclein 1-103 fragment.
Conclusions:
- The alpha-synuclein 1-103 fragment induces mitochondrial dysfunction contributing to PD.
- 7,8-dihydroxyflavone (7,8-DHF) demonstrates therapeutic potential for Parkinson's disease by protecting mitochondria.
- 7,8-DHF is a promising oral therapeutic candidate for PD treatment.
