Curcumin-induced upregulation of the anti-tau cochaperone BAG2 in primary rat cortical neurons

• Published in: Neuroscience letters Vol. 554; pp. 121 - 125
• Main Authors: Patil, Sachin P., Tran, Nhung, Geekiyanage, Hirosha, Liu, Li, Chan, Christina
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 25.10.2013
• Subjects: Alzheimer's disease; Animals; BAG2; Catechin - analogs & derivatives; Catechin - pharmacology; Cerebral Cortex - cytology; Curcumin; Curcumin - pharmacology; Lysosomal Membrane Proteins - metabolism; Molecular Chaperones - metabolism; Neurons - drug effects; Neurons - metabolism; Polyphenol; Primary Cell Culture; Rats; Resveratrol; Stilbenes - pharmacology; Tau; tau Proteins - metabolism; Up-Regulation; APP; AD; EGCG; ADAM10; Tau; BACE1; Aβ; LDH; OA; Polyphenol; NFTs; BAG2; LAMP1; ROS; AMPK; Curcumin; Alzheimer's disease; beta-site APP cleaving enzyme-1; AMP-activated protein kinase; okadaic acid; (−)-epigallocatechin-3-gallate; amyloid precursor protein; reactive oxygen species; lysosomal-associated membrane protein 1; BCL2-associated athanogene 2; lactate dehydrogenase; a disintegrin and metalloproteinase domain 10; amyloid beta; neurofibillary tangles
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2013.09.008

•We studied effects of curcumin, EGCG and resveratrol on BAG2 and LAMP1 levels.•All three compounds upregulated BAG2 levels at different concentrations.•EGCG also upregulated LAMP1 levels dose-dependently.•Curcumin downregulated phosphorylated tau levels in a cellular phosho-tau model. Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aβ) protein and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Various studies suggest that the tau tangle pathology, which lies downstream to Aβ pathology, is essential to produce AD-associated clinical phenotype and thus treatments targeting tau pathology may prevent or delay disease progression effectively. In this context, our present study examined three polyphenol compounds (curcumin, EGCG and resveratrol) for their possible activity against two endogenous proteins (BAG2 and LAMP1) that are shown to play a vital role in clearing tau tangles from neurons. Human epidemiological and animal data suggest potential positive effects of these polyphenols against AD. Here, primary rat cortical neurons treated with these polyphenols significantly up-regulated BAG2 levels at different concentrations, while only EGCG upregulated LAMP1 levels, although at higher concentrations. Importantly, curcumin doubled BAG2 levels at low micromolar concentrations that are clinically relevant. In addition, curcumin also downregulated levels of phosphorylated tau, which may be potentially attributed to the curcumin-induced upregulation in BAG2 levels in the neurons. The present results demonstrate novel activity of polyphenol curcumin in up-regulating an anti-tau cochaperone BAG2 and thus, suggest probable benefit of curcumin against AD-associated tauopathy.