Curcumin mediates presenilin-1 activity to reduce β-amyloid production in a model of Alzheimer's Disease.
Journal Title: Pharmacological Reports - Year 2011, Vol 63, Issue 5
Abstract
Curcumin has been reported to inhibit the generation of Aβ, but the underlying mechanisms by which this occurs remain unknown. Aβ is thought to play an important role in the pathogenesis of Alzheimer's disease (AD). The amyloid hypothesis argues that aggregates of Aβ trigger a complex pathological cascade that leads to neurodegeneration. Aβ is generated by the processing of APP (amyloid precursor protein) by β- and γ-secretases. Presenilin 1 (PS1) is central to γ-secretase activity and is a substrate for GSK-3β, both of which are implicated in the pathogenesis of AD. The present study aimed to investigate the effects of curcumin on the generation of Aβ in cultured neuroblastoma cells and on the in vitro expression of PS1 and GSK-3β. To stimulate Aβ production, a plasmid expressing APP was transfected into human SH-SY5Y neuroblastoma cells. The transfected cells were then treated with curcumin at 0-20 μM for 24 h or with 5 μM curcumin for 0-48 h, and the extracellular levels of Aβ(40/42) were determined by ELISA. The levels of PS1 and GSK-3β mRNA were measured by RT-PCR, and the expression of the PS1 and GSK-3β proteins (including the phosphorylated form of GSK-3β, p-GSK-3β-Ser9) were evaluated by western blotting. Curcumin treatment was found to markedly reduce the production of Aβ(40/42). Treatment with curcumin also decreased both PS1 and GSK-3β mRNA and protein levels in a dose- and time-dependent manner. Furthermore, curcumin increased the inhibitory phosphorylation of GSK-3β protein at Ser9. Therefore, we propose that curcumin decreases Aβ production by inhibiting GSK-3β-mediated PS1 activation.
Authors and Affiliations
Zhang Xiong, Si Lu, Li Yu
Keywords
Related Articles
- EP ID EP134842
- DOI -
- Views 87
- Downloads 0
In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation.
Background: Although several studies show that there is an increased risk of bleeding events during antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs), few studies show direct effects in vitro...
Lymphocyte-suppressing, endothelial-protective and systemic anti-inflammatory effects of metformin in fenofibrate-treated patients with impaired glucose tolerance.
Background: No previous clinical study has been designed to assess the additive effect of metformin and a fibrate on lymphocyte secretory function. The aim of our study was to investigate whether metformin produces any e...
Chronic impairment of the vagus nerve function leads to inhibition of dopamine but not serotonin neurons in rat brain structures.
BACKGROUNd: Recent clinical studies have shown that the dorsal motor nucleus of the vagus nerve is one of the brain areas that are the earliest affected by α-synuclein and Lewy body pathology in Parkinson's disease. This...
Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats.
Glucocorticoid-induced osteoporosis is the most frequently occurring type of secondary osteoporosis. Antagonists of β-adrenergic receptors are now considered to be potential drugs under investigation for osteoporosis. Th...
Effect of kindled seizures on rat behavior in water Morris maze test and amino acid concentrations in brain structures.
The effects of kindled seizures elicited by repeated pentetetrazole (PTZ) injections, on learning and memory in the Morris water maze test and on concentration of brain amino acids, were examined in rats. It was found th...