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Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease.

Authors :
Eo H
Yu SH
Choi Y
Kim Y
Kang YC
Lee H
Kim JH
Han K
Lee HK
Chang MY
Oh MS
Kim CH
Source :
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics [Neurotherapeutics] 2024 Jul; Vol. 21 (4), pp. e00355. Date of Electronic Publication: 2024 Apr 04.
Publication Year :
2024

Abstract

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transfer on PD in vitro and in vivo. The results showed that PN-101 mitochondria isolated from human mesenchymal stem cells exhibited a neuroprotective effect against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and rotenone in dopaminergic cells and ameliorated dopaminergic neuronal loss in the brains of C57BL/6J mice injected 30 ​mg/kg of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, PN-101 exhibited anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines in microglial cells and suppressing microglial activation in the striatum. Furthermore, intravenous mitochondrial treatment was associated with behavioral improvements during the pole test and rotarod test in the MPTP-induced PD mice. These dual effects of neuroprotection and anti-neuroinflammation support the potential for mitochondrial transplantation as a novel therapeutic strategy for PD.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shin-Hye Yu reports a relationship with Paean Biotechnology that includes: employment. Yujin Kim reports a relationship with Paean Biotechnology that includes: employment. Young Cheol Kang reports a relationship with Paean Biotechnology that includes: equity or stocks. Kyuboem Han reports a relationship with Paean Biotechnology that includes: employment. Hong Kyu Lee reports a relationship with Paean Biotechnology that includes: employment. Chun-Hyung Kim reports a relationship with Paean Biotechnology that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1878-7479
Volume :
21
Issue :
4
Database :
MEDLINE
Journal :
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
Publication Type :
Academic Journal
Accession number :
38580511
Full Text :
https://doi.org/10.1016/j.neurot.2024.e00355