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Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy. Nanomedicine 2017 Apr;13(3):809-820

Date

10/25/2016

Pubmed ID

27771430

Pubmed Central ID

PMC5392427

DOI

10.1016/j.nano.2016.10.004

Scopus ID

2-s2.0-85013270036 (requires institutional sign-in at Scopus site)   83 Citations

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.

Author List

Brenza TM, Ghaisas S, Ramirez JEV, Harischandra D, Anantharam V, Kalyanaraman B, Kanthasamy AG, Narasimhan B

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetophenones
Animals
Antioxidants
Cell Line
Cells, Cultured
Drug Carriers
Drug Delivery Systems
Humans
Mice
Mitochondria
Nanoparticles
Neurons
Neuroprotection
Oxidative Stress
Polyanhydrides