Acetyl-L-carnitine protects against amyloid-beta neurotoxicity: roles of oxidative buffering and ATP levels.
Acetyl-L-carnitine (ALCAR), normally produced in mitochondria, is a precursor of acetyl-CoA in the tricarboxylic (TCA) cycle. Since mitochondrial compromise and ATP depletion have been considered to play a role in neuronal degeneration in Alzheimer's disease (AD), we examined whether ALCAR attenuated oxidative stress and/or ATP depletion after exposure of cells to beta-amyloid (Abeta), a neurotoxic peptide that accumulates in AD brain. Differentiated SH-SY-5Y human neuroblastoma cells were exposed for 2-24 h to 20 microM Abeta in the presence and absence of 50 microM ALCAR. ALCAR attenuated oxidative stress and cell death induced by Abeta neurotoxicity. Abeta depleted ATP levels, suggesting Abeta may induce neurotoxicity in part by compromising neuronal energy. ALCAR prevented ATP depletion; therefore, ALCAR may mediate its protective effect by buffering oxidative stress and maintaining ATP levels.
Center for Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, Massachusetts 01854, USA. Thomas_Shea@uml.edu
Sirakarnt
S
Dhitavat
Daniela
D
Ortiz
Thomas B
TB
Shea
Ezequiel R
ER
Rivera
D000108:Acetylcarnitine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D000108:Acetylcarnitine; D000255:Adenosine Triphosphate