The AAPS Journal

, Volume 8, Issue 3, pp E521–E531

Mitochondria-targeted peptide antioxidants: Novel neuroprotective agents


DOI: 10.1208/aapsj080362

Cite this article as:
Szeto, H.H. AAPS J (2006) 8: E521. doi:10.1208/aapsj080362


Increasing evidence suggests that mitochondrial dysfunction and oxidative stress play a crucial role in the majority of neurodegenerative diseases. Mitochondria are a major source of intracellular reactive oxygen species (ROS) and are particularly vulnerable to oxidative stress. Oxidative damage to mitochondria has been shown to impair mitochondrial function and lead to cell death via apoptosis and necrosis. Because dysfunctional mitochondria will produce more ROS, a feed-forward loop is set up whereby ROS-mediated oxidative damage to mitochondria favors more ROS generation, resulting in a vicious cycle. It is now appreciated that reduction of mitochondrial oxidative stress may prevent or slow down the progression of these neurodegenerative disorders. However, if mitochondria are the major source of intracellular ROS and mitochondria are most vulnerable to oxidative damage, then it would be ideal to deliver the antioxidant therapy to mitochondria. This review will summarize the development of a novel class of mitochondria-targeted antioxidants that can protect mitochondria against oxidative stress and prevent neuronal cell death in animal models of stroke, Parkinson’s disease, and amyotrophic lateral sclerosis.


Reactive oxygen species mitochondrial permeability transition apoptosis necrosis Parkinson’s disease amyotrophic lateral sclerosis 

Copyright information

© American Association of Pharmaceutical Scientists 2006

Authors and Affiliations

  1. 1.Department of PharmacologyJoan and Sanford I. Weill Medical College of Cornell UniversityNew York

Personalised recommendations