Indoor VOCs exposure induced Parkinson-like behaviors through autophagy dysfunction and NLRP3 inflammasome-mediated neuroinflammation

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  • 作者:Jie Zheng, Yaxian Pang, Yaling Zhang, Wentao Hu, Peihao Yang, Qingping Liu, Jie Ning, Zhe Du, Xiaoting Jin, Jinglong Tang, Yujie Niu, Yuxin Zheng, Rong Zhang
  • 期刊:JOURNAL OF HAZARDOUS MATERIALS
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Indoor volatile organic compounds (VOCs) exposure has been associated with a variety of human diseases, including neurological disorders. However, studies on VOCs-induced Parkinson's disease (PD) and its underlying mechanisms are limited. We established a simulated real indoor VOCs combined inhalation mouse model to investigate the adverse effects of indoor VOCs on dopaminergic nervous system and the potential toxicological mechanisms. Our results demonstrated that VOCs exposure induced alpha-synuclein (α-syn) aggregation and degeneration of dopaminergic neurons and nerve terminals, and then led to PD-like behaviors in a time-dependent manner. VOCs combined exposure disrupted lysosomal function and led to autophagy dysfunction, which in turn resulted in NLRP3 (NOD-, LRR-, and pyrin-domain containing protein 3) inflammasome-mediated excessive neuroinflammation, thus leading to dopaminergic neuron death, which was associated with the pathogenesis of PD.

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