Exosomes from patients with Parkinson's disease are pathological in mice.

Abstract

Cell-to-cell transport of risk molecules is a highly anticipated pathogenic mechanism in the initiation and progression of various neurodegenerative diseases. Extracellular exosome-mediated neuron to neuron transport of α-synuclein (α-syn) is increasingly recognized as a potential etiologic mechanism in Parkinson's disease (PD). Exosomal inflammation has also been increasingly implicated in PD pathogenesis and could trigger, facilitate, or aggravate disease development. However, these mechanisms have not been verified systematically, especially in vivo. Since serum contains abundant exosomes, the correlation between serum exosomes and PD pathogenesis remains unknown. Here, we show that exosomes from PD patient serum contain more α-syn and inflammatory factors such as IL-1β and TNF-α than neurological normal controls, eventually cause α-syn, ubiquitin, and P62 aggregation in recipient cells. More importantly, the intravenous or intrastriatal treatment of mice with exosomes from PD patient serum could evoke protein aggregation, trigger dopamine neuron degeneration, induce microglial activation, and cause apomorphine-coaxed rotation and movement defects. All these findings imply the exosome pathway as a new pathogenesis mechanism for PD, and therefore may present new targets for therapeutics. KEY MESSAGES: We have presented the evidence for a relationship between PD (Parkinson's disease) patients' serum exosomes and pathogenesis. PD patients' serum-derived exosomes could induce α-syn, ubiquitin and P62 aggregation in recipient cells. Intravenous or intrastriatal treatments of mice with PD exosomes were able to recapitulate the molecular, cellular and behavioral phenotypes of PD.

• Authors: Chao Han, Nian Xiong, Xingfang Guo, Jinsha Huang, Kai Ma, Ling Liu, Yun Xia, Yan Shen, Jie Li, Haiyang Jiang, Luxi Wang, Shiyi Guo, Xiaoyun Xu, Guoxin Zhang, Jingyu Liu, Xuebing Cao, Zhentao Zhang, Zhicheng Lin, Tao Wang
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 97 Issue 9 Pg. 1329-1344 (09 2019) ISSN: 1432-1440 [Electronic] Germany
• PMID: 31302715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Synuclein

Topics

• Animals
• Disease Progression
• Exosomes (metabolism, pathology)
• Humans
• Inflammation (metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Microglia (metabolism, pathology)
• Parkinson Disease (metabolism, pathology)
• alpha-Synuclein (metabolism)