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Acetyl-L-carnitine may be useful as a therapeutic strategy for patients with Alzheimer disease
NewsRx.com
10-11-06
Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity.
Investigators in the United States report, "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and cognition and by senile plaques and neurofibrillary tangles in brain. Amyloid-beta peptide, particularly the 42-amino-acid peptide (A beta(1-42)), is a principal component of senile plaques and is thought to be central to the pathogenesis of the disease."
"The AD brain is under significant oxidative stress, and A beta(1-42) peptide is known to cause oxidative stress in vitro and in vivo. Acetyl-L-carnitine (ALCAR) is an endogenous mitochondrial membrane compound that helps to maintain mitochondrial bioenergetics and lowers the increased oxidative stress associated with aging. Glutathione (GSH) is an important endogenous antioxidant, and its levels have been shown to decrease with aging. Administration of ALCAR increases cellular levels of GSH in rat astrocytes," wrote H.M. Abdul and colleagues, University of Kentucky.
"In the current study, we investigated whether ALCAR plays a protective role in cortical neuronal cells against A beta(1-42)-mediated oxidative stress and neurotoxicity. Decreased cell survival in neuronal cultures treated with A beta(1-42) correlated with an increase in protein oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (4-hydroxy-2-nonenal) formation. Pretreatment of primary cortical neuronal cultures with ALCAR significantly attenuated A beta(1-42)-induced cytotoxicity, protein oxidation, lipid peroxidation, and apoptosis in a dose-dependent manner. Addition of ALCAR to neurons also led to an elevated cellular GSH and heat shock proteins (HSPs) levels compared with untreated control cells.
"Our results suggest that ALCAR exerts protective effects against A beta(1-42) toxicity and oxidative stress in part by up-regulating the levels of GSH and HSPs. This evidence supports the pharmacological potential of acetyl carnitine in the management of A beta(1-42)-induced oxidative stress and neurotoxicity," the researchers summarized.
"Therefore, ALCAR may be useful as a possible therapeutic strategy for patients with AD," the authors concluded.
Abdul and colleagues published their study in the Journal of Neuroscience Research (Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease. J Neurosci Res, 2006;84(2):398-408).
For additional information, contact D.A. Butterfield, University of Kentucky, Dept. of Chemical, Center Membrane Science, Lexington, KY 40506, USA.
The publisher of the Journal of Neuroscience Research can be contacted at: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.
NewsRx.com
10-11-06
Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity.
Investigators in the United States report, "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and cognition and by senile plaques and neurofibrillary tangles in brain. Amyloid-beta peptide, particularly the 42-amino-acid peptide (A beta(1-42)), is a principal component of senile plaques and is thought to be central to the pathogenesis of the disease."
"The AD brain is under significant oxidative stress, and A beta(1-42) peptide is known to cause oxidative stress in vitro and in vivo. Acetyl-L-carnitine (ALCAR) is an endogenous mitochondrial membrane compound that helps to maintain mitochondrial bioenergetics and lowers the increased oxidative stress associated with aging. Glutathione (GSH) is an important endogenous antioxidant, and its levels have been shown to decrease with aging. Administration of ALCAR increases cellular levels of GSH in rat astrocytes," wrote H.M. Abdul and colleagues, University of Kentucky.
"In the current study, we investigated whether ALCAR plays a protective role in cortical neuronal cells against A beta(1-42)-mediated oxidative stress and neurotoxicity. Decreased cell survival in neuronal cultures treated with A beta(1-42) correlated with an increase in protein oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (4-hydroxy-2-nonenal) formation. Pretreatment of primary cortical neuronal cultures with ALCAR significantly attenuated A beta(1-42)-induced cytotoxicity, protein oxidation, lipid peroxidation, and apoptosis in a dose-dependent manner. Addition of ALCAR to neurons also led to an elevated cellular GSH and heat shock proteins (HSPs) levels compared with untreated control cells.
"Our results suggest that ALCAR exerts protective effects against A beta(1-42) toxicity and oxidative stress in part by up-regulating the levels of GSH and HSPs. This evidence supports the pharmacological potential of acetyl carnitine in the management of A beta(1-42)-induced oxidative stress and neurotoxicity," the researchers summarized.
"Therefore, ALCAR may be useful as a possible therapeutic strategy for patients with AD," the authors concluded.
Abdul and colleagues published their study in the Journal of Neuroscience Research (Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease. J Neurosci Res, 2006;84(2):398-408).
For additional information, contact D.A. Butterfield, University of Kentucky, Dept. of Chemical, Center Membrane Science, Lexington, KY 40506, USA.
The publisher of the Journal of Neuroscience Research can be contacted at: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.
