Document Type
Article
Language
Eng
Publication Date
11-2017
Publisher
Mary Ann Liebert Inc.
Source Publication
Antioxidants & Redox Signaling
Source ISSN
1523-0864
Abstract
Aims: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor deficits and degeneration of dopaminergic neurons. Caused by a number of genetic and environmental factors, mitochondrial dysfunction and oxidative stress play a role in neurodegeneration in PD. By selectively knocking out mitochondrial transcription factor A (TFAM) in dopaminergic neurons, the transgenic MitoPark mice recapitulate many signature features of the disease, including progressive motor deficits, neuronal loss, and protein inclusions. In the present study, we evaluated the neuroprotective efficacy of a novel mitochondrially targeted antioxidant, Mito-apocynin, in MitoPark mice and cell culture models of neuroinflammation and mitochondrial dysfunction.
Results: Oral administration of Mito-apocynin (10 mg/kg, thrice a week) showed excellent central nervous system bioavailability and significantly improved locomotor activity and coordination in MitoPark mice. Importantly, Mito-apocynin also partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apo improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation.
Innovation: The properties of Mito-apocynin identified in the MitoPark transgenic mouse model strongly support potential clinical applications for Mito-apocynin as a viable neuroprotective and anti-neuroinflammatory drug for treating PD when compared to conventional therapeutic approaches.
Conclusion: Collectively, our data demonstrate, for the first time, that a novel orally active apocynin derivative improves behavioral, inflammatory, and neurodegenerative processes in a severe progressive dopaminergic neurodegenerative model of PD. Antioxid. Redox Signal. 27, 1048–1066.
Recommended Citation
Langley, Monica; Ghosh, Anamitra; Charli, Adhithiya; Sarkar, Souvarish; Ay, Muhammet; Luo, Jie; Zielonka, Jacek; Brenza, Timothy; Bennett, Brian; Jin, Huajun; Ghaisas, Shivani; Schlichtmann, Benjamin; Kim, Dongsuk; Anantharam, Vellareddy; Kanthasamy, Arthi; Narasimhan, Balaji; Kalyanaraman, Balaraman; and Kanthasamy, Anumantha G., "Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice" (2017). Physics Faculty Research and Publications. 148.
https://epublications.marquette.edu/physics_fac/148
Comments
Accepted version. "Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice," in Antioxidants & Redox Signaling, Vol. 27, No. 14 (November 2017): 1048-1066. DOI. © 2017 Mary Ann Liebert Inc. Used with permission