Folate, vitamin E, and acetyl-L-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid-beta.
Oxidative stress is an early and pivotal factor in Alzheimer's disease (AD). The neurotoxic peptide amyloid-beta (Abeta) contributes to oxidative damage in AD by inducing lipid peroxidation, which in turn generates additional downstream cytosolic free radicals and reactive oxygen species (ROS), leading to mitochondrial and cytoskeletal compromise, depletion of ATP, and ultimate apoptosis. Timely application of antioxidants can prevent all downstream consequences of Abeta exposure in culture, but in situ efficacy is limited, due in part to prior damage as well as difficulty in delivery. Herein, we demonstrate that administration of a combination of vitamin E (which prevents de novo membrane oxidative damage), folate (which maintains levels of the endogenous antioxidant glutathione), and acetyl-L-carnitine (which prevents Abeta-induced mitochondrial damage and ATP depletion) provides superior protection to that derived from each agent alone. These findings support a combinatorial approach in Alzheimer's therapy.
Dhitavat
Sirikarnt
S
Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts-Lowell, Lowell, MA 01854, USA.
Ortiz
Daniela
D
Rogers
Eugene
E
Rivera
Ezequiel
E
Shea
Thomas B
TB
D000108:Acetylcarnitine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017382:Reactive Oxygen Species; D014815:Vitamins; D014810:Vitamin E; D000108:Acetylcarnitine; D000255:Adenosine Triphosphate; D005492:Folic Acid