No abstract

Alzheimer's disease is characterized by the abnormal aggregation of amyloid-beta peptide (Abeta) in extracellular deposits known as senile plaques. However, the nature of the toxic Abeta species and its precise mechanism of action remain unclear. Previous reports suggest that the histidine residues are involved in copper-Abeta interaction, by which resulting in the neurotoxicity of Abeta and free radical damage. Here, we employed a mutant Abeta (Abeta H13R) in which a histidine residue was replaced by arginine. Copper facilitated the precipitation of both wild-type and mutant Abeta in the spectrophotometric absorbance assay but suppressed beta-structure aggregates according to Thioflavine-T assay. Wild-type Abeta alone is more cytotoxic but produced less amount of H(2)O(2) than AbetaH13R-copper complexes, suggesting that Abeta-membrane interaction may also implicated in the pathologic progress. Abeta toxicity is in positive correlation to its competence to aggregate despite the aggregation is mainly composed of non-beta fibril substances. In short, these findings may provide further evidence on the role of copper in the pathogenesis of Alzheimer's disease.

Alzheimer’s disease (AD) is characterized by a large number of amyloid-β (Aβ) deposits in the brain. Therefore, inhibiting Aβ aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects. Recent study shows that COS could markedly decrease oligomeric Aβ-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce Aβ-mediated neurotoxicity remains unclear. In the present study, our findings from circular dichroism spectroscopy, transmission electron microscope and thioflavin T fluorescence assay suggested that COS act as an inhibitor of Aβ aggregation and this effect shows dose-dependency. Moreover, data from thioflavin T assay indicated that COS could significantly inhibit fibrils formation and disrupt preformed fibrils in a dose-dependent manner. Furthermore, the addition of COS attenuated Aβ1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit Aβ1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-Aβ fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD.

No abstract

This study assessed the modulating effects of liquiritin against cognitive deficits, oxidative damage, and neuronal apoptosis induced by subsequent bilateral intrahippocampal injections of aggregated amyloid-β (Aβ). This study also explored the molecular mechanisms underlying the above phenomena. Liquiritin was orally administered to rats with Aβ-induced cognitive deficits for 2 weeks. The protective effects of liquiritin on the learning and memory impairment induced by Aβ were examined in vivo by using Morris water maze. The rats were then euthanized for further studies. The antioxidant activities of liquiritin in the hippocampus of the rats were investigated by biochemical and immunohistochemical methods. The apoptosis of the neurons was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. Liquiritin at doses of 50-100 mg/kg significantly improved the cognitive ability, restored the abnormal activities of glutathione peroxidase and superoxide dismutase, and decreased the levels of malondialdehyde，8-hydroxy-2'-deoxyguanosine and protein carbonyl in the hippocampus of rats with Alzheimer's disease. Moreover, neural apoptosis in the hippocampus of Aβ-treated rats was reversed by liquiritin. Liquiritin can significantly ameliorate Aβ-induced spatial learning and memory impairment by inhibiting oxidative stress and neural apoptosis.