Antioxidant gene therapy against neuronal cell death

Authors

Juliana Navarro-Yepes, University of Nebraska-Lincoln
Laura Zavala-Flores, University of Nebraska-Lincoln
Anandhan Annadurai, University of Nebraska-LincolnFollow
Fang Wang, University of Nebraska-Lincoln
Maciej Skotak, University of Nebraska-LincolnFollow
Namas Chandra, University of Nebraska-Lincoln
Ming Li, University of Nebraska-LincolnFollow
Aglaia Pappa, Democritus University of Thrace
Daniel Martinez-Fong, CINVESTAV–IPN, Mexico City, Mexico
Luz Maria Del Razo, CINVESTAV–IPN, Mexico City, Mexico
Betzabet Quintanilla-Vega, CINVESTAV–IPN, Mexico City, Mexico
Rodrigo Franco, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

5-2014

Citation

Published in final edited form as: Pharmacology & Therapeutics 142:2 (May 2014), pp. 206–230; doi:10.1016/j.pharmthera.2013.12.007.

Comments

Copyright 2013 Elsevier Inc. Used by permission. PubMed Central version.

Abstract

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated inmitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy.