Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy.

Abstract

A progressive loss of neuronal structure and function is a signature of many neurodegenerative conditions including chronic traumatic encephalopathy, Parkinson's, Huntington's and Alzheimer's diseases. Mitochondrial dysfunction and oxidative and nitrative stress have been implicated as key pathological mechanisms underlying the neurodegenerative processes. However, current therapeutic approaches targeting oxidative damage are ineffective in preventing the progression of neurodegeneration. Mitochondria-targeted antioxidants were recently shown to alleviate oxidative damage. In this work, we investigated the delivery of biodegradable polyanhydride nanoparticles containing the mitochondria-targeted antioxidant apocynin to neuronal cells and the ability of the nano-formulation to protect cells against oxidative stress. The nano-formulated mitochondria-targeted apocynin provided excellent protection against oxidative stress-induced mitochondrial dysfunction and neuronal damage in a dopaminergic neuronal cell line, mouse primary cortical neurons, and a human mesencephalic cell line. Collectively, our results demonstrate that nano-formulated mitochondria-targeted apocynin may offer improved efficacy of mitochondria-targeted antioxidants to treat neurodegenerative disease.

• Authors: Timothy M Brenza, Shivani Ghaisas, Julia E Vela Ramirez, Dilshan Harischandra, Vellareddy Anantharam, Balaraman Kalyanaraman, Anumantha G Kanthasamy, Balaji Narasimhan
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 13 Issue 3 Pg. 809-820 (04 2017) ISSN: 1549-9642 [Electronic] United States
• PMID: 27771430 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Acetophenones
• Antioxidants
• Drug Carriers
• Polyanhydrides
• acetovanillone

Topics

• Acetophenones (administration & dosage, pharmacology)
• Animals
• Antioxidants (administration & dosage, pharmacology)
• Cell Line
• Cells, Cultured
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Humans
• Mice
• Mitochondria (drug effects, metabolism)
• Nanoparticles (chemistry, ultrastructure)
• Neurons (drug effects, metabolism)
• Neuroprotection (drug effects)
• Oxidative Stress (drug effects)
• Polyanhydrides (chemistry)