Manganese Porphyrin Reduces Oxidative Stress in Vulnerable Parkin-Null Drosophila Dopaminergic Neurons

Authors

Amber N. Juba, Biomedical Sciences Program, Midwestern University, Glendale, AZ 85308, USA.
Petros P. Keoseyan, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA.
Riley P. Hamel, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA.
Tigran Margaryan, Department of Translational Neuroscience, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Michaela L. Barber, Biomedical Sciences Program, Midwestern University, Glendale, AZ 85308, USA.
Amanda N. Foley, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA.
T Bucky Jones, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA.
Ines Batinic-Haberle, Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Artak Tovmasyan, Department of Translational Neuroscience, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Lori M. Buhlman, Biomedical Sciences Program, Midwestern University, Glendale, AZ 85308, USA.

Document Type

Article

Abstract

Oxidative stress and mitochondrial dysfunction are heavily implicated in all forms of Parkinson's disease; however, antioxidant administration has largely failed in clinical trials. Among the likely causes of failure are brain bioavailability and cellular redox state. We have administered two manganese porphyrin compounds with different bioavailability, MnTE-2-PyP and MnTnBuOE-2-PyP, to parkin-null Drosophila food and found that the more bioavailable one, with higher brain and mitochondrial availability, MnTnBuOE-2-PyP, improves developmental deficits and motivated behavior in female flies. Using highly sensitive redox reporters, we further found that MnTnBuOE-2-PyP reduces hydrogen peroxide levels in mitochondria of dopaminergic neurons that are functionally homologous to the mammalian substantia nigra and facilitates motivated behavior in female flies. Interestingly, both compounds reduce an oxidative stress marker at the whole-brain level and extend lifespan in control flies. Neither compound improves lifespan in parkin-null flies. Thus, additional studies, changing the timing and/or dosage of compound administration, are warranted.

Keywords

Drosophila, antioxidants, dopaminergic neuron, glutathione, hydrogen peroxide, manganese porphyrin, mitochondria, oxidative stress, parkin, redox

Publication Date

8-22-2025

Publication Title

Antioxidants (Basel, Switzerland)

ISSN

2076-3921

Volume

14

Issue

9

PubMed ID

41008938

Digital Object Identifier (DOI)

10.3390/antiox14091031

Recommended Citation

Juba, Amber N.; Keoseyan, Petros P.; Hamel, Riley P.; Margaryan, Tigran; Barber, Michaela L.; Foley, Amanda N.; Jones, T Bucky; Batinic-Haberle, Ines; Tovmasyan, Artak; and Buhlman, Lori M., "Manganese Porphyrin Reduces Oxidative Stress in Vulnerable Parkin-Null Drosophila Dopaminergic Neurons" (2025). Translational Neuroscience. 2469.
https://scholar.barrowneuro.org/neurobiology/2469