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Analyzing the Parkinson's Disease Mouse Model Induced by Adeno-associated Viral Vectors Encoding Human α-Synuclein
Published on: July 29, 2022
Crosstalk between exosomes and cellular senescence: A core vicious loop promoting α-synuclein pathology in
Wenwei Mao1, Wenhao Song2, Yuhan Zhang1
1College of Clinical Medicine, Jining Medical University, Jining, Shandong Province, China.
Abstract:
Parkinson's disease is characterized by α-synuclein aggregation, dopaminergic neuron loss, and neuroinflammation. Emerging evidence reveals complex crosstalk between exosomes and cellular senescence in Parkinson's disease pathogenesis. Exosomes mediate α-synuclein transmission and neuroinflammation, while delivering protective factors such as miRNAs that inhibit cellular senescence. Senescent cells secrete pro-inflammatory factors via mitochondrial dysfunction and the senescence-associated secretory phenotype, linking to Parkinson's disease mitophagy defects. This forms a vicious "senescence-protein deposition-inflammation" cycle, with senescent cell-derived exosomes exacerbating α-synuclein aggregation and inflammation. Therapeutically, exosomes are ideal drug carriers due to blood-brain barrier penetrability and low immunogenicity for targeted antioxidant delivery. Future perspectives highlight exosome-based biomarkers and brain-gut axis intervention as promising directions. We propose integrating exosome engineering and senolytic strategies to lay the foundation for early diagnosis and precision therapy of Parkinson's disease, promoting diagnosis-intervention translational research and bridging bench-tobedside translation.
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