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Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice

Antioxidants & redox signaling, 2017-11, Vol.27 (14), p.1048-1066 [Peer Reviewed Journal]

(©) Copyright 2017, Mary Ann Liebert, Inc. ;Copyright 2017, Mary Ann Liebert, Inc. 2017 ;ISSN: 1523-0864 ;EISSN: 1557-7716 ;DOI: 10.1089/ars.2016.6905 ;PMID: 28375739

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Title:
Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice
Author: 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 ; Kanthasamy, Anumantha G
Subjects: Acetophenones - administration & dosage ; Acetophenones - chemistry ; Acetophenones - pharmacology ; Activation ; Administration, Oral ; Animal models ; Animals ; Antioxidants ; Antioxidants - administration & dosage ; Antioxidants - pharmacology ; Bioavailability ; Cell culture ; Cells, Cultured ; Central nervous system ; CYBB protein ; Damage detection ; Damage prevention ; Degeneration ; Disease Models, Animal ; DNA-Binding Proteins - genetics ; Dopamine receptors ; Environmental factors ; Gene Knockout Techniques ; High Mobility Group Proteins - genetics ; Humans ; Inflammation ; Innovations ; Locomotor activity ; Mice ; Mice, Transgenic ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Movement disorders ; Muridae ; NADPH Oxidase 2 - metabolism ; Neurodegeneration ; Neurodegenerative diseases ; Neurons ; Neuroprotection ; Oral administration ; Original Research Communications ; Oxidative stress ; Oxidative Stress - drug effects ; Parkinson Disease - drug therapy ; Parkinson Disease - metabolism ; Parkinson's disease ; Rodents ; Therapeutic applications ; Transgenic mice
Is Part Of: Antioxidants & redox signaling, 2017-11, Vol.27 (14), p.1048-1066
Description: 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. 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. 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. 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.
Publisher: United States: Mary Ann Liebert, Inc
Language: English
Identifier: ISSN: 1523-0864
EISSN: 1557-7716
DOI: 10.1089/ars.2016.6905
PMID: 28375739
Source: MEDLINE
Alma/SFX Local Collection

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Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice

(©) Copyright 2017, Mary Ann Liebert, Inc. ;Copyright 2017, Mary Ann Liebert, Inc. 2017 ;ISSN: 1523-0864 ;EISSN: 1557-7716 ;DOI: 10.1089/ars.2016.6905 ;PMID: 28375739

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