Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis.

Abstract

Reactive oxygen species (ROS) play a major role in the pathogenesis of neurodegenerative diseases. They are important contributors to necrotic and apoptotic cell death. A major proportion of cellular ROS is generated at the inner mitochondrial membrane by the respiratory chain. In the present study, we investigated a novel peptide antioxidant (SS-31) targeted to the inner mitochondrial membrane for its therapeutic effects both in vitro and in vivo in the G93A mouse model of amyotrophic lateral sclerosis (ALS). SS-31 protected against cell death induced by hydrogen peroxide in vitro in neuronal cells stably transfected with either wild-type or mutant Cu/Zn superoxide dismutase (SOD1). Daily intraperitoneal injections of SS-31 (5 mg/kg), starting at 30 days of age, led to a significant improvement in survival and motor performance. In comparison with vehicle-treated G93A mice, SS-31-treated mice showed a decreased cell loss and a decrease in immunostaining for markers of oxidative stress in the lumbar spinal cord. This further enhances the concept that pharmacological modification of oxidative stress is a therapeutic option for the treatment of ALS.

• Authors: Susanne Petri, Mahmoud Kiaei, Maria Damiano, Andrew Hiller, Elizabeth Wille, Giovanni Manfredi, Noel Y Calingasan, Hazel H Szeto, M Flint Beal
• Journal: Journal of neurochemistry (J Neurochem) Vol. 98 Issue 4 Pg. 1141-8 (Aug 2006) ISSN: 0022-3042 [Print] England
• PMID: 16895581 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Peptides
• Reactive Oxygen Species
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Aging (physiology)
• Amyotrophic Lateral Sclerosis (drug therapy, pathology)
• Animals
• Antioxidants (metabolism, therapeutic use)
• Body Weight (physiology)
• Cell Count
• Cell Membrane Permeability
• Cells, Cultured
• Disease Models, Animal
• Mice
• Mice, Transgenic
• Peptides (metabolism, therapeutic use)
• Psychomotor Performance (physiology)
• Reactive Oxygen Species (metabolism)
• Spinal Cord (pathology)
• Superoxide Dismutase (genetics, metabolism)
• Superoxide Dismutase-1