Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide.
ABSTRACT Amyloid beta-peptide (Abeta) is heavily deposited in the brains of Alzheimer's disease (AD) patients. Free-radical oxidative stress, particularly of neuronal lipids, proteins and DNA, is extensive in those AD brain areas in which Abeta is abundant. Recent research suggests that these observations might be linked, and it is postulated that Abeta-induced oxidative stress leads to neurodegeneration in AD brain. Consonant with this postulate, Abeta leads to neuronal lipid peroxidation, protein oxidation and DNA oxidation by means that are inhibited by free-radical antioxidants. Here, we summarize current research on phospholipid peroxidation, as well as protein and DNA oxidation, in AD brain, and discuss the potential role of Abeta in this oxidative stress.
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ABSTRACT: The antioxidative and neuroprotective effects of Loranthus parasiticus (L.) Merr (Loranthaceae) were investigated for the first time. L. parasiticus ethanol extract (LPEE), L. parasiticus ethyl acetate fraction (LPEAF), and L. parasiticus aqueous fraction (LPAF) were evaluated and exhibited antioxidative activity in a dose-dependent manner. LPAF exhibited the lowest IC 50 values of 16.82 ± 0.27 μg/ml and 1.05 ± 0.04 mg/ml in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and lipid peroxidation activities, respectively. Moreover, LPAF possessed the strongest reducing power activity and the highest total phenolic content. The neuroprotective activity was investigated in NG108-15 hybridoma cells against hydrogen peroxide (H 2 O 2)-induced oxidative stress by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Both LPEE and LPAF exhibited neuroprotective activity on NG108-15 cells in a dose-dependent manner with the highest cell viability (78.00 ± 1.85%) observed with LPAF at the highest treatment concentration of 100 μg/ml. A close correlation was evident between antioxidative and neuroprotective activities with the total phenolic content in LPAF. These results suggested that LPAF may be used as a potent antioxidant and neuroprotectant in treating or preventing neurodegenerative diseases where oxidative stress is implicated.
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ABSTRACT: Mulberry, which contained high amounts of anthocyanins, has been used in traditional Chinese medicine. Mulberry fruit extracts (ME) have demonstrated the antioxidant activity and neuroprotection. The study was to investigate the neuroprotective efficacy of ME against β-amyloid 25-35- (Aβ 25-35-) induced PC12 cells injury. Cells preincubated with or without ME (200 μg/mL) for 24 h were treated with Aβ 25-35 (20 μmol/L) for another 24 h. Cell viability was assessed by MTT, gene expression profiles were examined by cDNA microarrays, and RT-PCR were used to confirm the results of microarray assays. ME pretreatment was found to neutralize the cytotoxicity and prevent Aβ 25-35-induced cells injury. Analyses of gene expression profile revealed that genes involving cell adhesion, peptidase activity, cytokine activity, ion binding activity, and angiogenesis regulation were significantly modulated by ME pretreatment. Among those genes, Apaf1, Bace2, and Plcb4 were enriched in the "Alzheimer's disease-reference pathway" and downregulated after ME intervention. RT-PCR results showed that ME preincubation could significantly inhibit Aβ 25-35 increased mRNA levels of these three genes. Overall, ME pretreatment could substantially alleviate PC12 cells injury and downregulate expression of AD-related genes, such as Apaf1, Bace2, and Plcb4. This study has a great nutrigenomics interest and brings new and important light in the field of AD intervention.Evidence-based complementary and alternative medicine : eCAM. 01/2014; 2014:150617.
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ABSTRACT: We explore the role of DNA damage processing in the progression of cognitive decline by creating a new mouse model. The new model is a cross of a common Alzheimer's disease (AD) mouse (3xTgAD), with a mouse that is heterozygous for the critical DNA base excision repair enzyme, DNA polymerase ␤. A reduc-tion of this enzyme causes neurodegeneration and aggravates the AD features of the 3xTgAD mouse, in-ducing neuronal dysfunction, cell death and impair-ing memory and synaptic plasticity. Transcriptional profiling revealed remarkable similarities in gene ex-pression alterations in brain tissue of human AD pa-tients and 3xTg/Pol␤ +/− mice including abnormal-ities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in base excision repair capacity can render the brain more vulnerable to AD-related molecular and cellular alterations.Nucleic Acids Research 12/2014; · 8.81 Impact Factor