title: Curcumin-induced upregulation of the anti-tau cochaperone BAG2 in primary rat cortical neurons.
abstract: 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.
authors.affiliation: Cellular and Biomolecular Laboratory, Department of Chemical Engineering and Material Science, Michigan State University, East Lansing, MI 48824, USA. Electronic address: spatil@widener.edu.
authors.forename: Sachin P
authors.initials: SP
authors.lastname: Patil
authors.forename: Nhung
authors.initials: N
authors.lastname: Tran
authors.forename: Hirosha
authors.initials: H
authors.lastname: Geekiyanage
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D003474:Curcumin / Q000494:pharmacology*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D015854:Up-Regulation; D016875:tau Proteins / Q000378:metabolism*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D002392:Catechin; D003474:Curcumin; D051907:Lysosomal Membrane Proteins; D018832:Molecular Chaperones; D000077185:Resveratrol; D013267:Stilbenes; D016875:tau Proteins; C588369:BAG2 protein, rat; C489117:Lamp1 protein, rat; D052118:Lysosomal-Associated Membrane Protein 1; C045651:epigallocatechin gallate
keywords: (−)-epigallocatechin-3-gallate; AD; ADAM10; AMP-activated protein kinase; AMPK; APP; Alzheimer's disease; Aβ; BACE1; BAG2; BCL2-associated athanogene 2; Curcumin; EGCG; LAMP1; LDH; NFTs; OA; Polyphenol; ROS; Tau; a disintegrin and metalloproteinase domain 10; amyloid beta; amyloid precursor protein; beta-site APP cleaving enzyme-1; lactate dehydrogenase; lysosomal-associated membrane protein 1; neurofibillary tangles; okadaic acid; reactive oxygen species
references.citation: Neuropathol Appl Neurobiol. 2006 Oct;32(5):505-16
references.pmid: 16972884
references.citation: Neurosci Lett. 1993 Apr 16;153(1):57-60
references.pmid: 7685510
references.citation: Mol Cell. 2007 Jul 6;27(1):91-105
references.pmid: 17612493
references.citation: J Alzheimers Dis. 2010;20(4):1189-99
references.pmid: 20413894
references.citation: Genes Nutr. 2009 Dec;4(4):283-96
references.pmid: 19756809
references.citation: Nature. 2000 May 18;405(6784):360-4
references.pmid: 10830966
references.citation: CNS Neurosci Ther. 2010 Oct;16(5):285-97
references.pmid: 20406252
references.citation: Brain Res. 2008 Jun 12;1214:177-87
references.pmid: 18457818
references.citation: Rev Neurol (Paris). 1997 Apr;153(3):185-92
references.pmid: 9296132
references.citation: Neuroreport. 2008 Aug 27;19(13):1329-33
references.pmid: 18695518
references.citation: Nature. 2004 Aug 5;430(7000):631-9
references.pmid: 15295589
references.citation: Nat Genet. 2005 May;37(5):495-500
references.pmid: 15806104
references.citation: J Neurosci. 2011 May 25;31(21):7817-30
references.pmid: 21613495
references.citation: Biochem J. 2004 Sep 1;382(Pt 2):481-9
references.pmid: 15200388
references.citation: Neuroreport. 2007 Feb 12;18(3):297-300
references.pmid: 17314675
references.citation: J Biomed Biotechnol. 2009;2009:871313
references.pmid: 19707536
references.citation: Mol Neurobiol. 2010 Jun;41(2-3):392-409
references.pmid: 20437209
references.citation: Int J Dev Neurosci. 2012 Oct;30(6):411-9
references.pmid: 22906543
references.citation: EMBO J. 2007 Jul 11;26(13):3169-79
references.pmid: 17581637
references.citation: J Inorg Biochem. 2007 Sep;101(9):1265-9
references.pmid: 17629564
references.citation: J Neurochem. 1993 Apr;60(4):1578-81
references.pmid: 8455043
references.citation: FEBS Lett. 2010 Oct 8;584(19):4259-67
references.pmid: 20849853
references.citation: J Neurochem. 2010 Mar;112(6):1415-30
references.pmid: 20050972
references.citation: Neurosci Lett. 2005 Aug 26;384(3):288-93
references.pmid: 15939536
references.citation: Neurology. 1992 Mar;42(3 Pt 1):631-9
references.pmid: 1549228
references.citation: J Neurosci. 2009 Feb 18;29(7):2151-61
references.pmid: 19228967
references.citation: FASEB J. 2011 Jan;25(1):219-31
references.pmid: 20852062
references.citation: Brain Pathol. 1998 Apr;8(2):387-402
references.pmid: 9546295