Astragalin confers coordinated neuroprotection in Parkinson's disease models through modulation of neurotrophic, anti-inflammatory, and synuclein-related pathways.
Astragalin confers coordinated neuroprotection in Parkinson's disease models through modulation of neurotrophic, anti-inflammatory, and synuclein-related pathways.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Beijing, CN · Author affiliation
Key Laboratory of Ecology and Environment in Minority Areas National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China.Location evidence
Shenzhen, CN · Author affiliation
Department of Biochemistry & Cell Biology, School of Basic Medical Sciences, Shenzhen University School of Medicine, Shenzhen, 518060, China. Electronic address: lan@szu.edu.cn.Location evidence
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Original abstract
Parkinson's disease (PD) remains a neurodegenerative disorder without effective disease-modifying therapies, largely due to its multifactorial pathogenesis. We report that the natural flavonoid Astragalin (AST) concurrently addresses three core pathological processes in PD, namely dopaminergic neuron degeneration, α-synucleinopathy, and neuroinflammation, through coordinated modulation of interconnected molecular pathways. In both subacute MPTP- and chronic rotenone-induced murine PD models, AST preserved 85% of nigral tyrosine hydroxylase-positive neurons, fully prevented motor deficits, and suppressed phosphorylated α-synuclein (α-Syn) accumulation and Lewy body-like inclusion formation. Mechanistically, AST activated the BDNF-TrkB/AKT pro-survival pathway, enhanced NRF2-mediated antioxidant defense, and suppressed neuroinflammatory cascades by dual inhibition of Notch1/HES-1 and COP1-C/EBPβ signaling, leading to attenuated microglial and astrocytic activation. These findings position AST as a promising multi-target therapeutic neuroprotective candidate with disease-modifying potential, providing a structural scaffold for developing combination-inspired anti-PD strategies.