title: Intravenous administration of mitochondria for treating experimental Parkinson's disease.
abstract: Mitochondrial dysfunction is associated with a large number of human diseases, including neurological and muscular degeneration, cardiovascular disorders, obesity, diabetes, aging and rare mitochondrial diseases. Replacement of dysfunctional mitochondria with functional exogenous mitochondria is proposed as a general principle to treat these diseases. Here we found that mitochondria isolated from human hepatoma cell could naturally enter human neuroblastoma SH-SY5Y cell line, and when the mitochondria were intravenously injected into mice, all of the mice were survived and no obvious abnormality appeared. The results of in vivo distribution suggested that the exogenous mitochondria distributed in various tissues including brain, liver, kidney, muscle and heart, which would benefit for multi-systemically mitochondrial diseases. In normal mice, mitochondrial supplement improved their endurance by increase of energy production in forced swimming test; and in experimental Parkinson's disease (PD) model mice induced by respiratory chain inhibitor MPTP, mitochondrial replacement prevented experimental PD progress through increasing the activity of electron transport chain, decreasing reactive oxygen species level, and preventing cell apoptosis and necrosis. Since effective drugs remain elusive to date for mitochondrial diseases, the strategy of mitochondrial replacement would provide an essential and innovative approach as mitochondrial therapy.
authors.affiliation: School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Xianxun
authors.initials: X
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fu
authors.affiliation: School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China. Electronic address: fal@swu.edu.cn.
authors.forename: Ailing
authors.initials: A
authors.lastname: Fu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001688:Biological Products / Q000008:administration & dosage*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria; D010300:Parkinson Disease / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D001688:Biological Products
keywords: Cell uptake; In vivo distribution; Intravenous injection; Mitochondrial diseases; Mitochondrial therapy