Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrP res accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases.
References
[1]
Prusiner, S.B. Prions. Proc. Natl. Acad. Sci. USA 1998, 95, 13363–13383, doi:10.1073/pnas.95.23.13363.
Brown, P.; Preece, M.; Brandel, J.P.; Sato, T.; McShane, L.; Zerr, I.; Fletcher, A.; Will, R.G.; Pocchiari, M.; Cashman, N.R.; et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000, 55, 1075–1081, doi:10.1212/WNL.55.8.1075.
[4]
Caughey, B.; Raymond, L.D.; Raymond, G.J.; Maxson, L.; Silveira, J.; Baron, G.S. Inhibition of protease-resistant prion protein accumulation in vitro by curcumin. J. Virol. 2003, 77, 5499–5502, doi:10.1128/JVI.77.9.5499-5502.2003.
[5]
Hafner-Bratkovic, I.; Gaspersic, J.; Smid, L.M.; Bresjanac, M.; Jerala, R. Curcumin binds to the alpha-helical intermediate and to the amyloid form of prion protein - a new mechanism for the inhibition of PrP(Sc) accumulation. J. Neurochem. 2008, 104, 1553–1564, doi:10.1111/j.1471-4159.2007.05105.x.
[6]
Basnet, P.; Skalko-Basnet, N. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules 2011, 16, 4567–4598, doi:10.3390/molecules16064567.
[7]
Buchanan, M.M.; Hutchinson, M.; Watkins, L.R.; Yin, H. Toll-like receptor 4 in CNS pathologies. J. Neurochem. 2010, 114, 13–27.
[8]
Yang, F.; Lim, G.P.; Begum, A.N.; Ubeda, O.J.; Simmons, M.R.; Ambegaokar, S.S.; Chen, P.P.; Kayed, R.; Glabe, C.G.; Frautschy, S.A.; et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem. 2005, 280, 5892–5901.
[9]
Caughey, B.; Race, R.E. Potent inhibition of scrapie-associated PrP accumulation by congo red. J. Neurochem. 1992, 59, 768–771, doi:10.1111/j.1471-4159.1992.tb09437.x.
[10]
Demaimay, R.; Harper, J.; Gordon, H.; Weaver, D.; Chesebro, B.; Caughey, B. Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. J. Neurochem. 1998, 71, 2534–2541.
[11]
Federico, A.; Cardaioli, E.; Da Pozzo, P.; Formichi, P.; Gallus, G.N.; Radi, E. Mitochondria, oxidative stress and neurodegeneration. J. Neurol. Sci. 2012, 322, 254–262, doi:10.1016/j.jns.2012.05.030.
[12]
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006, 443, 787–795, doi:10.1038/nature05292.
[13]
Ollivier Milhavet, S.L. Oxidative stress and the prion protein in transmissible spongiform encephalopathies. Brain Res. Rev. 2002, 38, 328–339, doi:10.1016/S0165-0173(01)00150-3.
[14]
Bocharova, O.V.; Breydo, L.; Parfenov, A.S.; Salnikov, V.V.; Baskakov, I.V. In vitro conversion of full-length mammalian prion protein produces amyloid form with physical properties of PrP(Sc). J. Mol. Biol. 2005, 346, 645–659, doi:10.1016/j.jmb.2004.11.068.
[15]
Luo, J.C.; Wang, S.C.; Jian, W.B.; Chen, C.H.; Tang, J.L.; Lee, C.I. Formation of amyloid fibrils from beta-amylase. FEBS Lett. 2012, 586, 680–685, doi:10.1016/j.febslet.2012.01.062.
[16]
Schagger, H. Tricine-SDS-PAGE. Nat. Protoc. 2006, 1, 16–22, doi:10.1038/nprot.2006.4.
[17]
Sunde, M.; Blake, C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 1997, 50, 123–159, doi:10.1016/S0065-3233(08)60320-4.
Williams, T.L.; Serpell, L.C. Membrane and surface interactions of Alzheimer's Abeta peptide--insights into the mechanism of cytotoxicity. FEBS J. 2011, 278, 3905–3917, doi:10.1111/j.1742-4658.2011.08228.x.
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: Problems and promises. Mol.Pharmaceut. 2007, 4, 807–818, doi:10.1021/mp700113r.
[22]
Institute, N.C. Clinical development plan: Curcumin. J. Cell. Biochem. Suppl. 1996, 26, 72–85.
[23]
Cheng, A.L.; Hsu, C.H.; Lin, J.K.; Hsu, M.M.; Ho, Y.F.; Shen, T.S.; Ko, J.Y.; Lin, J.T.; Lin, B.R.; Ming-Shiang, W.; et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21, 2895–2900.
[24]
Chandra, V.; Pandav, R.; Dodge, H.H.; Johnston, J.M.; Belle, S.H.; DeKosky, S.T.; Ganguli, M. Incidence of Alzheimer's disease in a rural community in India: The Indo-US study. Neurology 2001, 57, 985–989, doi:10.1212/WNL.57.6.985.
[25]
Baum, L.; Lam, C.W.; Cheung, S.K.; Kwok, T.; Lui, V.; Tsoh, J.; Lam, L.; Leung, V.; Hui, E.; Ng, C.; et al. ix-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J. Clin. Psychopharmacol. 2008, 28, 110–113, doi:10.1097/jcp.0b013e318160862c.
[26]
Bounhar, Y.; Zhang, Y.; Goodyer, C.G.; LeBlanc, A. Prion protein protects human neurons against Bax-mediated apoptosis. J.Biol. Chem. 2001, 276, 39145–39149, doi:10.1074/jbc.C100443200.
[27]
Shmerling, D.; Hegyi, I.; Fischer, M.; Blattler, T.; Brandner, S.; Gotz, J.; Rulicke, T.; Flechsig, E.; Cozzio, A.; von Mering, C.; et al. Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 1998, 93, 203–214, doi:10.1016/S0092-8674(00)81572-X.
[28]
Kim, J.I.; Ju, W.K.; Choi, J.H.; Choi, E.; Carp, R.I.; Wisniewski, H.M.; Kim, Y.S. Expression of cytokine genes and increased nuclear factor-kappa B activity in the brains of scrapie-infected mice. Brain Res. Mol. Brain Res. 1999, 73, 17–27, doi:10.1016/S0169-328X(99)00229-6.
[29]
Perez, M.; Rojo, A.I.; Wandosell, F.; Diaz-Nido, J.; Avila, J. Prion peptide induces neuronal cell death through a pathway involving glycogen synthase kinase 3. Biochem. J. 2003, 372, 129–136, doi:10.1042/BJ20021596.
[30]
Huang, H.C.; Xu, K.; Jiang, Z.F. Curcumin-mediated neuroprotection against amyloid-beta-induced mitochondrial dysfunction involves the inhibition of GSK-3beta. J. Alzheimers. Dis. 2012, 32, 981–996.
