Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy. Nanomedicine 2017 Apr;13(3):809-820
Date
10/25/2016Pubmed ID
27771430Pubmed Central ID
PMC5392427DOI
10.1016/j.nano.2016.10.004Scopus ID
2-s2.0-85013270036 (requires institutional sign-in at Scopus site) 83 CitationsAbstract
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 BAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetophenonesAnimals
Antioxidants
Cell Line
Cells, Cultured
Drug Carriers
Drug Delivery Systems
Humans
Mice
Mitochondria
Nanoparticles
Neurons
Neuroprotection
Oxidative Stress
Polyanhydrides