Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2014, Article ID 425496, 15 pages
http://dx.doi.org/10.1155/2014/425496
Research Article

Cucurbitacin E Has Neuroprotective Properties and Autophagic Modulating Activities on Dopaminergic Neurons

1Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7
2Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, 500 50 Hradec Kralove, Czech Republic
3Institute of Earth Systems, University of Malta, Msida MSD 2080, Malta
4Department of Psychiatry and Neuroscience, Laval University and CHU Research Center, Québec, QC, Canada G1W 1C2

Received 25 July 2014; Revised 14 November 2014; Accepted 16 November 2014; Published 9 December 2014

Academic Editor: Liang-Jun Yan

Copyright © 2014 Anne-Marie Arel-Dubeau et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. A. Butterfield and J. Kanski, “Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins,” Mechanisms of Ageing and Development, vol. 122, no. 9, pp. 945–962, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. A. H. V. Schapira and M. Gegg, “Mitochondrial contribution to parkinson's disease pathogenesis,” Parkinson's Disease, vol. 2011, Article ID 159160, 7 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Gandhi and A. Y. Abramov, “Mechanism of oxidative stress in neurodegeneration,” Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 428010, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. W. Dauer and S. Przedborski, “Parkinson's disease: mechanisms and models,” Neuron, vol. 39, no. 6, pp. 889–909, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. P. M. Keeney, J. Xie, R. A. Capaldi, and J. P. Bennett Jr., “Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled,” Journal of Neuroscience, vol. 26, no. 19, pp. 5256–5264, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. A. H. Schapira and P. Jenner, “Etiology and pathogenesis of Parkinson's disease,” Movement Disorders, vol. 26, no. 6, pp. 1049–1055, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. J. Narkiewicz, G. Giachin, and G. Legname, “In vitro aggregation assays for the characterization of α-synuclein prion-like properties,” Prion, vol. 8, no. 1, pp. 19–32, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. D. C. Rubinsztein, M. DiFiglia, N. Heintz et al., “Autophagy and its possible roles in nervous system diseases, damage and repair.,” Autophagy, vol. 1, no. 1, pp. 11–22, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. B. Boland and R. A. Nixon, “Neuronal macroautophagy: from development to degeneration,” Molecular Aspects of Medicine, vol. 27, no. 5-6, pp. 503–519, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. D. Butler, R. A. Nixon, and B. A. Bahr, “Potential compensatory responses through autophagic/lysosomal pathways in neurodegenerative diseases,” Autophagy, vol. 2, no. 3, pp. 234–237, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Banerjee, M. F. Beal, and B. Thomas, “Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications,” Trends in Neurosciences, vol. 33, no. 12, pp. 541–549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. G. Twig, A. Elorza, A. J. A. Molina et al., “Fission and selective fusion govern mitochondrial segregation and elimination by autophagy,” EMBO Journal, vol. 27, no. 2, pp. 433–446, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. P. Muñoz, S. Huenchuguala, I. Paris, and J. Segura-Aguilar, “Dopamine oxidation and autophagy,” Parkinson's Disease, vol. 2012, Article ID 920953, 13 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. M. G. Spillantini, R. A. Crowther, R. Jakes, M. Hasegawa, and M. Goedert, “α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 11, pp. 6469–6473, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. G. Krebiehl, S. Ruckerbauer, L. F. Burbulla et al., “Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1,” PLoS ONE, vol. 5, no. 2, Article ID e9367, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. L. Alvarez-Erviti, M. C. Rodriguez-Oroz, J. M. Cooper et al., “Chaperone-mediated autophagy markers in Parkinson disease brains,” Archives of Neurology, vol. 67, no. 12, pp. 1464–1472, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. D. Narendra, A. Tanaka, D.-F. Suen, and R. J. Youle, “Parkin is recruited selectively to impaired mitochondria and promotes their autophagy,” The Journal of Cell Biology, vol. 183, no. 5, pp. 795–803, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. I. Irrcher, H. Aleyasin, E. L. Seifert et al., “Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics,” Human Molecular Genetics, vol. 19, no. 19, pp. 3734–3746, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. J.-Y. Lee, Y. Nagano, J. P. Taylor, K. L. Lim, and T.-P. Yao, “Disease-causing mutations in Parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy,” The Journal of Cell Biology, vol. 189, no. 4, pp. 671–679, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. J. H. Son, J. H. Shim, K.-H. Kim, J.-Y. Ha, and J. Y. Han, “Neuronal autophagy and neurodegenerative diseases,” Experimental and Molecular Medicine, vol. 44, no. 2, pp. 89–98, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Segura-Aguilar and R. M. Kostrzewa, “Neurotoxins and neurotoxic species implicated in neurodegeneration,” Neurotoxicity Research, vol. 6, no. 7-8, pp. 615–630, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Zuo and M. S. Motherwell, “The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease,” Gene, vol. 532, no. 1, pp. 18–23, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Blanchet, F. Longpré, G. Bureau et al., “Resveratrol, a red wine polyphenol, protects dopaminergic neurons in MPTP-treated mice,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 32, no. 5, pp. 1243–1250, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. J. Blesa, S. Phani, V. Jackson-Lewis, and S. Przedborski, “Classic and new animal models of Parkinson's disease,” Journal of Biomedicine and Biotechnology, vol. 2012, Article ID 845618, 10 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. V. Annese, M.-T. Herrero, M. Di Pentima et al., “Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism,” Brain Structure and Function, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Schober, “Classic toxin-induced animal models of Parkinson's disease: 6-OHDA and MPTP,” Cell and Tissue Research, vol. 318, no. 1, pp. 215–224, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Przedborski, K. Tieu, C. Perier, and M. Vila, “MPTP as a mitochondrial neurotoxic model of Parkinson's disease,” Journal of Bioenergetics and Biomembranes, vol. 36, no. 4, pp. 375–379, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Gélinas and M.-G. Martinoli, “Neuroprotective effect of estradiol and phytoestrogens on MPP+-induced cytotoxicity in neuronal PC12 cells,” Journal of Neuroscience Research, vol. 70, no. 1, pp. 90–96, 2002. View at Publisher · View at Google Scholar · View at Scopus
  29. K. B. Pandey and S. I. Rizvi, “Plant polyphenols as dietary antioxidants in human health and disease,” Oxidative Medicine and Cellular Longevity, vol. 2, no. 5, pp. 270–278, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Iriti, S. Vitalini, G. Fico, and F. Faoro, “Neuroprotective herbs and foods from different traditional medicines and diets,” Molecules, vol. 15, no. 5, pp. 3517–3555, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. N. A. Kelsey, H. M. Wilkins, and D. A. Linseman, “Nutraceutical antioxidants as novel neuroprotective agents,” Molecules, vol. 15, no. 11, pp. 7792–7814, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. H. C. Campos, M. D. D. Rocha, F. P. D. Viegas et al., “The role of natural products in the discovery of new drug candidates for the treatment of neurodegenerative disorders I: Parkinson's disease,” CNS and Neurological Disorders—Drug Targets, vol. 10, no. 2, pp. 239–250, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. B. J. Small, K. S. Rawson, C. Martin et al., “Nutraceutical intervention improves older adults' cognitive functioning,” Rejuvenation Research, vol. 17, no. 1, pp. 27–32, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. S. E. Seidl, J. A. Santiago, H. Bilyk, and J. A. Potashkin, “The emerging role of nutrition in Parkinson's disease,” Frontiers in Aging Neuroscience, vol. 6, article 36, pp. 1–13, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Stefani and S. Rigacci, “Beneficial properties of natural phenols: highlight on protection against pathological conditions associated with amyloid aggregation,” BioFactors, vol. 40, no. 5, pp. 482–493, 2014. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Tannin-Spitz, M. Bergman, and S. Grossman, “Cucurbitacin glucosides: antioxidant and free-radical scavenging activities,” Biochemical and Biophysical Research Communications, vol. 364, no. 1, pp. 181–186, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Sun, M. A. Blaskovich, R. Jove, S. K. Livingston, D. Coppola, and S. M. Sebti, “Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity,” Oncogene, vol. 24, no. 20, pp. 3236–3245, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. S. I. Abdelwahab, L. E. A. Hassan, H. M. Sirat et al., “Anti-inflammatory activities of cucurbitacin e isolated from Citrullus lanatus var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme inhibition,” Fitoterapia, vol. 82, no. 8, pp. 1190–1197, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. B. Jayaprakasam, N. P. Seeram, and M. G. Nair, “Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana,” Cancer Letters, vol. 189, no. 1, pp. 11–16, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. W.-W. Huang, J.-S. Yang, M.-W. Lin et al., “Cucurbitacin E induces G2/M phase arrest through STAT3/p53/p21 signaling and provokes apoptosis via Fas/CD95 and mitochondria-dependent pathways in human bladder cancer T24 cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 952762, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. E. Attard and A. Cuschieri, “Cytotoxicity of Cucurbitacin E extracted from Ecballium elateriumin vitro,” Journal of Natural Remedies, vol. 4, no. 2, pp. 137–144, 2004. View at Google Scholar · View at Scopus
  42. P. M. Sörensen, R. E. Iacob, M. Fritzsche et al., “The natural product cucurbitacin E inhibits depolymerization of actin filaments,” ACS Chemical Biology, vol. 7, no. 9, pp. 1502–1508, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. E. Attard, A. Cuschieri, and M. P. Brincat, “Morphological effects induced by Cucurbitacin E on ovarian cancer cells in vitro,” Journal of Natural Remedies, vol. 5, no. 1, pp. 70–74, 2005. View at Google Scholar · View at Scopus
  44. K. L. K. Duncan, M. D. Duncan, M. C. Alley, and E. A. Sausville, “Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells,” Biochemical Pharmacology, vol. 52, no. 10, pp. 1553–1560, 1996. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Momma, Y. Masuzawa, N. Nakai et al., “Direct interaction of Cucurbitacin E isolated from Alsomitra macrocarpa to actin filament,” Cytotechnology, vol. 56, no. 1, pp. 33–39, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. E. Attard, “Rapid detection of cucurbitacins in tissues and in vitro cultures of Ecballium elaterium (L.) A. Rich,” CGC Reports, vol. 25, pp. 71–75, 2002. View at Google Scholar
  47. J. Bournival, M.-A. Francoeur, J. Renaud, and M.-G. Martinoli, “Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis,” Rejuvenation Research, vol. 15, no. 3, pp. 322–333, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Bournival, P. Quessy, and M. G. Martinoli, “Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons,” Cellular and Molecular Neurobiology, vol. 29, no. 8, pp. 1169–1180, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Yamamoto, Y. Tagawa, T. Yoshimori, Y. Moriyama, R. Masaki, and Y. Tashiro, “Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells,” Cell Structure and Function, vol. 23, no. 1, pp. 33–42, 1998. View at Publisher · View at Google Scholar · View at Scopus
  50. I. G. Ganley, P.-M. Wong, N. Gammoh, and X. Jiang, “Disctinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest,” Molecular Cell, vol. 42, no. 6, pp. 731–743, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. C. H. Jung, S.-H. Ro, J. Cao, N. M. Otto, and D.-H. Kim Do-Hyung, “mTOR regulation of autophagy,” FEBS Letters, vol. 584, no. 7, pp. 1287–1295, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Haslam, D. Wyatt, and P. A. Kitos, “Estimating the number of viable animal cells in multi-well cultures based on their lactate dehydrogenase activities,” Cytotechnology, vol. 32, no. 1, pp. 63–75, 2000. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Bournival, M. Plouffe, J. Renaud, C. Provencher, and M.-G. Martinoli, “Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system,” Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 921941, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. O. S. Frankfurt and A. Krishan, “Identification of apoptotic cells by formamide-induced DNA denaturation in condensed chromatin,” Journal of Histochemistry and Cytochemistry, vol. 49, no. 3, pp. 369–378, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Carange, F. Longpré, B. Daoust, and M. G. Martinoli, “24-epibrassinolide, a phytosterol from the brassinosteroid family, protects dopaminergic cells against MPP+-induced oxidative stress and apoptosis,” Journal of Toxicology, vol. 2011, Article ID 392859, 13 pages, 2011. View at Publisher · View at Google Scholar
  56. P. Wardman, “Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects,” Free Radical Biology and Medicine, vol. 43, no. 7, pp. 995–1022, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Wrona, K. Patel, and P. Wardman, “Reactivity of 2′,7′-dichlorodihydrofluorescein and dihydrorhodamine 123 and their oxidized forms toward carbonate, nitrogen dioxide, and hydroxyl radicals,” Free Radical Biology and Medicine, vol. 38, no. 2, pp. 262–270, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. I. Tanida, T. Ueno, and E. Kominami, “LC3 and autophagy,” Methods in Molecular Biology, vol. 445, pp. 77–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. N. Mizushima and T. Yoshimori, “How to interpret LC3 immunoblotting,” Autophagy, vol. 3, no. 6, pp. 542–545, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. C. Lin, S.-C. Tsai, M. T. Tseng et al., “AKT serine/threonine protein kinase modulates baicalin-triggered autophagy in human bladder cancer T24 cells,” International Journal of Oncology, vol. 42, no. 3, pp. 993–1000, 2013. View at Publisher · View at Google Scholar · View at Scopus
  61. D. M. Arduíno, A. R. Esteves, L. Cortes et al., “Mitochondrial metabolism in Parkinson's disease impairs quality control autophagy by hampering microtubule-dependent traffic,” Human Molecular Genetics, vol. 21, no. 21, pp. 4680–4702, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Bugaut, M. Bruchard, H. Berger et al., “Bleomycin exerts ambivalent antitumor immune effect by triggering both immunogenic cell death and proliferation of regulatory T cells,” PLoS ONE, vol. 8, no. 6, Article ID e65181, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. C. L. Oeste, E. Seco, W. F. Patton, P. Boya, and D. Pérez-Sala, “Interactions between autophagic and endo-lysosomal markers in endothelial cells,” Histochemistry and Cell Biology, vol. 139, no. 5, pp. 659–670, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Zhou, Y. Huang, and S. Przedborski, “Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance,” Annals of the New York Academy of Sciences, vol. 1147, pp. 93–104, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. V. P.-D. L. Cruz, D. Elinos-Calderón, P. Carrillo-Mora et al., “Time-course correlation of early toxic events in three models of striatal damage: modulation by proteases inhibition,” Neurochemistry International, vol. 56, no. 6-7, pp. 834–842, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Dehay, J. Bové, N. Rodríguez-Muela et al., “Pathogenic lysosomal depletion in Parkinson's disease,” Journal of Neuroscience, vol. 30, no. 37, pp. 12535–12544, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. R. Köchl, X. W. Hu, E. Y. Chan, and S. A. Tooze, “Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes,” Traffic, vol. 7, no. 2, pp. 129–145, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. T. Zhang, J. Li, Y. Dong et al., “Cucurbitacin e inhibits breast tumor metastasis by suppressing cell migration and invasion,” Breast Cancer Research and Treatment, vol. 135, no. 2, pp. 445–458, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. Y.-C. Hsu, M.-J. Chen, and T.-Y. Huang, “Inducement of mitosis delay by cucurbitacin E, a novel tetracyclic triterpene from climbing stem of Cucumis melo L., through GADD45γ in human brain malignant glioma (GBM) 8401 cells,” Cell Death and Disease, vol. 5, no. 2, Article ID e1087, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. E. A. Attard, M. Scicluna-Spiteri, M. P. Brincat, and A. Cuschieri, “The effects of Cucurbitacin E on the proliferation of prostate and breast cancer cell lines, and peripheral T-lymphocytes,” Maltese Fourth Medical, School Conference, vol. R034, p. 145, 1999. View at Google Scholar
  71. J. Qiao, L. H. Xu, J. He, D. Y. Ouyang, and X. H. He, “Cucurbitacin E exhibits anti-inflammatory effect in RAW 264.7 cells via suppression of NF-κB nuclear translocation,” Inflammation Research, vol. 62, no. 5, pp. 461–469, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. F. Pietrocola, G. Mariño, D. Lissa et al., “Pro-autophagic polyphenols reduce the acetylation of cytoplasmic proteins,” Cell Cycle, vol. 11, no. 20, pp. 3851–3860, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Bureau, F. Longpré, and M.-G. Martinoli, “Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation,” Journal of Neuroscience Research, vol. 86, no. 2, pp. 403–410, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. D. K. Choi, S. Koppula, and K. Suk, “Inhibitors of microglial neurotoxicity: focus on natural products,” Molecules, vol. 16, no. 2, pp. 1021–1043, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. V. F. Cuzzola, R. Ciurleo, S. Giacoppo, S. Marino, and P. Bramanti, “Role of resveratrol and its analogues in the treatment of neurodegenerative diseases: focus on recent discoveries,” CNS & Neurological Disorders—Drug Targets, vol. 10, no. 7, pp. 849–862, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. V. Lahaie-Collins, J. Bournival, M. Plouffe, J. Carange, and M.-G. Martinoli, “Sesamin modulates tyrosine hydroxylase, superoxide dismutase, catalase, inducible NO synthase and interleukin-6 expression in dopaminergic cells under MPP+-induced oxidative stress,” Oxidative Medicine and Cellular Longevity, vol. 1, no. 1, pp. 54–62, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. N. Hamada, Y. Fujita, A. Tanaka et al., “Metabolites of sesamin, a major lignan in sesame seeds, induce neuronal differentiation in PC12 cells through activation of ERK1/2 signaling pathway,” Journal of Neural Transmission, vol. 116, no. 7, pp. 841–852, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. M. F. Blasina, L. Vaamonde, A. Morquio, C. Echeverry, F. Arredondo, and F. Dajas, “Differentiation induced by Achyrocline satureioides (Lam) infusion in PC12 cells,” Phytotherapy Research, vol. 23, no. 9, pp. 1263–1269, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. A. El Omri, J. Han, P. Yamada, K. Kawada, M. B. Abdrabbah, and H. Isoda, “Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2,” Journal of Ethnopharmacology, vol. 131, no. 2, pp. 451–458, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. J. Renaud, J. Bournival, X. Zottig, and M.-G. Martinoli, “Resveratrol Protects DAergic PC12 Cells from high glucose-induced oxidative stress and apoptosis: effect on p53 and GRP75 localization,” Neurotoxicity Research, vol. 25, no. 1, pp. 110–123, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Kadota, T. Yamaai, Y. Saito et al., “Expression of dopamine transporter at the tips of growing neurites of PC12 cells,” Journal of Histochemistry and Cytochemistry, vol. 44, no. 9, pp. 989–996, 1996. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Nilsen, G. Mor, and F. Naftolin, “Raloxifene induces neurite outgrowth in estrogen receptor positive PC12 cells,” Menopause, vol. 5, no. 4, pp. 211–216, 1998. View at Google Scholar · View at Scopus
  83. K. Chiasson, V. Lahaie-Collins, J. Bournival, B. Delapierre, S. Gélinas, and M.-G. Martinoli, “Oxidative stress and 17-α- and 17-β-estradiol modulate neurofilaments differently,” Journal of Molecular Neuroscience, vol. 30, no. 3, pp. 297–310, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Zhang, Y. Li, K. A. Park et al., “Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent apoptosis,” Autophagy, vol. 8, no. 4, pp. 559–576, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Xilouri, O. R. Brekk, D. Kirik, and L. Stefanis, “LAMP2A as a therapeutic target in Parkinson disease,” Autophagy, vol. 9, no. 12, pp. 2166–2168, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. F. Yang, Y.-P. Yang, C.-J. Mao et al., “Role of autophagy and proteasome degradation pathways in apoptosis of PC12 cells overexpressing human α-synuclein,” Neuroscience Letters, vol. 454, no. 3, pp. 203–208, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. T. Pan, S. Kondo, W. Le, and J. Jankovic, “The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease,” Brain, vol. 131, no. 8, pp. 1969–1978, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. L. Gao, T. Jiang, J. Guo et al., “Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats,” PLoS ONE, vol. 7, no. 9, Article ID e46092, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. F. Xu, J. Li, W. Ni, Y.-W. Shen, and X.-P. Zhang, “Peroxisome proliferator-activated receptor-γ agonist 15d-prostaglandin J2 mediates neuronal autophagy after cerebral ischemia-reperfusion injury,” PLoS ONE, vol. 8, no. 1, Article ID e55080, 2013. View at Publisher · View at Google Scholar · View at Scopus
  90. H. Appelqvist, P. Wäster, K. Kågedal, and K. Öllinger, “The lysosome: from waste bag to potential therapeutic target,” Journal of Molecular Cell Biology, vol. 5, no. 4, pp. 214–226, 2013. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Cartelli, C. Ronchi, M. G. Maggioni, S. Rodighiero, E. Giavini, and G. Cappelletti, “Microtubule dysfunction precedes transport impairment and mitochondria damage in MPP+-induced neurodegeneration,” Journal of Neurochemistry, vol. 115, no. 1, pp. 247–258, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. S. M. Cardoso, A. R. Esteves, and D. M. Arduno, “Mitochondrial metabolic control of microtubule dynamics impairs the autophagic pathway in Parkinson's disease,” Neurodegenerative Diseases, vol. 10, no. 1–4, pp. 38–40, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Demers-Lamarche, M. Grondin, A. P. Nguyen, and M. Germain, “KB1-regulated adaptive mechanisms are essential for clearance of protein aggregates and neuronal survival following mitochondrial dysfunction,” in Proceedings of the 5th Canadian Association for Neuroscience Meeting, poster no. 2-C-75, Montreal, Canada, May 2014.
  94. M. German and R. S. Slack, “Dining in with BCL-2: new guests at the autophagy table,” Clinical Science, vol. 118, no. 3, pp. 173–181, 2010. View at Publisher · View at Google Scholar · View at Scopus