About this Journal Submit a Manuscript Table of Contents
Oxidative Medicine and Cellular Longevity
Volume 2012 (2012), Article ID 240146, 12 pages
http://dx.doi.org/10.1155/2012/240146
Review Article

Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems

Department of Drug Sciences, Faculty of Pharmacy, G. d'Annunzio University, Via dei Vestini 31, 66100 Chieti, Italy

Received 7 February 2012; Accepted 22 March 2012

Academic Editor: Madia Trujillo

Copyright © 2012 Ivana Cacciatore 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. K. A. Jellinker, “General aspects of neurodegeneration,” Journal of Neural Transmission, vol. 65, pp. 101–144, 2003.
  2. K. A. Jellinger, “Basic mechanisms of neurodegeneration: a critical update,” Journal of Cellular and Molecular Medicine, vol. 14, no. 3, pp. 457–487, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Valko, D. Leibfritz, J. Moncol, M. T. D. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological functions and human disease,” International Journal of Biochemistry and Cell Biology, vol. 39, no. 1, pp. 44–84, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Melo, L. Monteiro, R. M. F. Lima, D. M. de Oliveira, M. D. de Cerqueira, and R. S. El-Bacha, “Oxidative stress in neurodegenerative diseases: mechanism and therapeutic perspectives,” Oxidative Medicine and Cellular Longevity, vol. 2011, Article ID 467180, 14 pages, 2011.
  5. W. R. Markesbery, “The role of oxidative stress in Alzheimer disease,” Archives of Neurology, vol. 56, no. 12, pp. 1449–1452, 1999. View at Scopus
  6. L. M. Sayre, M. A. Smith, and G. Perry, “Chemistry and biochemistry of oxidative stress in neurodegenerative disease,” Current Medicinal Chemistry, vol. 8, no. 7, pp. 721–738, 2001. View at Scopus
  7. J. T. Coyle and P. Puttfarcken, “Oxidative stress, glutamate, and neurodegenerative disorders,” Science, vol. 262, no. 5134, pp. 689–695, 1993. View at Scopus
  8. P. Jenner, “Oxidative stress in Parkinson's disease,” Annals of Neurology, vol. 53, supplement 3, pp. S26–S38, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. M. C. Polidori, H. R. Griffiths, E. Mariani, and P. Mecocci, “Hallmarks of protein oxidative damage in neurodegenerative diseases: focus on Alzheimer's disease,” Amino Acids, vol. 32, no. 4, pp. 553–559, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. P. I. Moreira, K. Honda, L. Quan et al., “Alzheimer's disease and oxidative stress: the old problem remains unsolved,” Current Medicinal Chemistry, vol. 5, no. 1, pp. 51–62, 2005. View at Scopus
  11. T. Farooqui and A. A. Farooqui, “Aging: an important factor for the pathogenesis of neurodegenerative diseases,” Mechanisms of Ageing and Development, vol. 130, no. 4, pp. 203–215, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Fahn and G. Cohen, “The oxidant stress hypothesis in Parkinson's disease: evidence supporting it,” Annals of Neurology, vol. 32, no. 6, pp. 804–812, 1992. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Offen, S. Gorodin, E. Melamed, J. Hanania, and Z. Malik, “Dopamine-melanin is actively phagocytized by PC12 cells and cerebellar granular cells: possible implications for the etiology of Parkinson's disease,” Neuroscience Letters, vol. 260, no. 2, pp. 101–104, 1999. View at Publisher · View at Google Scholar · View at Scopus
  14. J. B. Schulz, J. Lindenau, J. Seyfried, and J. Dichgans, “Glutathione, oxidative stress and neurodegeneration,” European Journal of Biochemistry, vol. 267, no. 16, pp. 4904–4911, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. J. S. Bains and C. A. Shaw, “Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death,” Brain Research Reviews, vol. 25, no. 3, pp. 335–358, 1997. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Lee, T. Cho, N. Jantaratnotai, Y. T. Wang, E. McGeer, and P. L. McGeer, “Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases,” The FASEB Journal, vol. 24, no. 7, pp. 2533–2545, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. R. K. B. Pearce, A. Owen, S. Daniel, P. Jenner, and C. D. Marsden, “Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease,” Journal of Neural Transmission, vol. 104, no. 6-7, pp. 661–677, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Sian, D. T. Dexter, A. J. Lees et al., “Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia,” Annals of Neurology, vol. 36, no. 3, pp. 348–355, 1994. View at Scopus
  19. P. Damier, E. C. Hirsch, P. Zhang, Y. Agid, and F. Javoy-Agid, “Glutathione peroxidase, glial cells and Parkinson's disease,” Neuroscience, vol. 52, no. 1, pp. 1–6, 1993. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Garrido, Y. Tereshchenko, Z. Zhevtsova, G. Taschenberger, M. Bähr, and S. Kügler, “Glutathione depletion and overproduction both initiate degeneration of nigral dopaminergic neurons,” Acta Neuropathologica, vol. 121, no. 4, pp. 475–485, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. D. S. Albers and M. F. Beal, “Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease,” Journal of Neural Transmission, no. 59, pp. 133–154, 2000. View at Scopus
  22. P. Jenner, “Oxidative mechanisms in nigral cell death in Parkinson's disease,” Movement Disorders, vol. 13, no. 1, pp. 24–34, 1998. View at Scopus
  23. J. P. E. Spencer, P. Jenner, S. E. Daniel, A. J. Lees, D. C. Marsden, and B. Halliwell, “Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species,” Journal of Neurochemistry, vol. 71, no. 5, pp. 2112–2122, 1998. View at Scopus
  24. J. K. Andersen, J. Q. Mo, D. G. Horn et al., “Effect of buthionine sulfoximine, a synthesis inhibitor of the antioxidant glutathione, on the murine nigrostriatal neurons,” Journal of Neurochemistry, vol. 67, no. 5, pp. 2164–2171, 1996. View at Scopus
  25. M. T. Lin and M. F. Beal, “Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases,” Nature, vol. 443, no. 7113, pp. 787–795, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. S. J. Chinta and J. K. Andersen, “Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease,” Free Radical Biology and Medicine, vol. 41, no. 9, pp. 1442–1448, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. S. J. Chinta, M. J. Kumar, M. Hsu et al., “Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degeneration,” Journal of Neuroscience, vol. 27, no. 51, pp. 13997–14006, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. L. F. Lau and M. A. Brodney, “Therapeutic approaches for the treatment of Alzheimer’s disease: an overview,” Topics in Medicinal Chemistry, vol. 2, pp. 1–24, 2008.
  29. S. Varadarajan, S. Yatin, M. Aksenova, and D. A. Butterfield, “Review: Alzheimer's amyloid β-peptide-associated free radical oxidative stress and neurotoxicity,” Journal of Structural Biology, vol. 130, no. 2-3, pp. 184–208, 2000. View at Publisher · View at Google Scholar · View at Scopus
  30. A. V. Maltsev, S. Bystryak, and O. V. Galzitskaya, “The role of β-amyloid peptide in neurodegenerative diseases,” Ageing Research Reviews, vol. 10, pp. 440–452, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Gu, A. D. Owen, S. E. K. Toffa et al., “Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases,” Journal of the Neurological Sciences, vol. 158, no. 1, pp. 24–29, 1998. View at Publisher · View at Google Scholar · View at Scopus
  32. H. Liu, L. E. Harrell, S. Shenvi, T. Hagen, and R. M. Liu, “Gender differences in glutathione metabolism in Alzheimer's disease,” Journal of Neuroscience Research, vol. 79, no. 6, pp. 861–867, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. J. D. Adams, L. K. Klaidman, I. N. Odunze, H. C. Shen, and C. A. Miller, “Alzheimer's and Parkinson's disease: brain levels of glutathione, glutathione disulfide, and vitamin E,” Molecular and Chemical Neuropathology, vol. 14, no. 3, pp. 213–226, 1991. View at Scopus
  34. T. L. Perry, V. W. Yong, C. Bergeron, S. Hansen, and K. Jones, “Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer’s disease,” Annals of Neurology, vol. 21, no. 4, pp. 331–336, 2005.
  35. R. J. Mark, M. A. Lovell, W. R. Markesbery, K. Uchida, and M. P. Mattson, “A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid β- peptide,” Journal of Neurochemistry, vol. 68, no. 1, pp. 255–264, 1997. View at Scopus
  36. D. A. Butterfield, C. B. Pocernich, and J. Drake, “Elevated glutathione as a therapeutic strategy in Alzheimer's disease,” Drug Development Research, vol. 56, no. 3, pp. 428–437, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. C. L. Hammond, T. K. Lee, and N. Ballatori, “Novel roles for glutathione in gene expression, cell death, and membrane transport of organic solutes,” Journal of Hepatology, vol. 34, no. 6, pp. 946–954, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. N. Ghosh, R. Ghosh, and S. C. Mandal, “Antioxidant protection: a promising therapeutic intervention in neurodegenerative disease,” Free Radical Research, vol. 45, no. 8, pp. 888–905, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. V. di Matteo and E. Esposito, “Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis,” Current Drug Targets, CNS & Neurological Disorders, vol. 2, no. 2, pp. 95–107, 2003. View at Scopus
  40. I. Cacciatore, C. Cornacchia, L. Baldassarre et al., “GPE and GPE analogues as promising neuroprotective agents,” Mini Reviews in Medicinal Chemistry, vol. 12, no. 1, pp. 13–23, 2012.
  41. C. Cornacchia, I. Cacciatore, L. Baldassarre, A. Mollica, F. Feliciani, and F. Pinnen, “2,5-Diketopiperazines as neuroprotective agents,” Mini Reviews in Medicinal Chemistry, vol. 12, pp. 2–12, 2012.
  42. B. Moosmann and C. Behl, “Antioxidants as treatment for neurodegenerative disorders,” Expert Opinion on Investigational Drugs, vol. 11, no. 10, pp. 1407–1435, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. R. Dringen, “Metabolism and functions of glutathione in brain,” Progress in Neurobiology, vol. 62, no. 6, pp. 649–671, 2000. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Dringen and J. Hirrlinger, “Glutathione pathways in the brain,” Biological Chemistry, vol. 384, no. 4, pp. 505–516, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. J. S. Bains and C. A. Shaw, “Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death,” Brain Research Reviews, vol. 25, no. 3, pp. 335–358, 1997. View at Publisher · View at Google Scholar · View at Scopus
  46. D. M. Townsend, K. D. Tew, and H. Tapiero, “The importance of glutathione in human disease,” Biomedicine and Pharmacotherapy, vol. 57, no. 3, pp. 145–155, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. N. Ballatori, S. M. Krance, S. Notenboom, S. Shi, K. Tieu, and C. L. Hammond, “Glutathione dysregulation and the etiology and progression of human diseases,” Biological Chemistry, vol. 390, no. 3, pp. 191–214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. H. L. Martin and P. Teismann, “Glutathione—a review on its role and significance in Parkinson's dysregulation and the etiology and progression of human diseases,” The FASEB Journal, vol. 23, pp. 3263–3272, 2009.
  49. I. Guidi, D. Galimberti, S. Lonati et al., “Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease,” Neurobiology of Aging, vol. 27, no. 2, pp. 262–269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Dumont and M. F. Beal, “Neuroprotective strategies involving ROS in Alzheimer disease,” Free Radical Biology and Medicine, vol. 51, pp. 1014–1026, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. M. J. Mcmanus, M. P. Murphy, and J. L. Franklin, “The mitochondria-targeted antioxidant mitoq prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer's disease,” The Journal of Neuroscience, vol. 31, pp. 15703–15715, 2011.
  52. J. S. Beckman, A. G. Estévez, J. P. Crow, and L. Barbeito, “Superoxide dismutase and the death of motoneurons in ALS,” Trends in Neurosciences, vol. 24, supplement 11, pp. S15–S20, 2001. View at Scopus
  53. M. R. Vargas, D. A. Johnson, and J. A. Johnson, “Decreased glutathione accelerates neurologiCal deficit and mitochondrial pathology in familial ALS-linked hSOD1G93A mice model,” Neurobiology of Disease, vol. 43, no. 3, pp. 543–551, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Behl and B. Moosmann, “Antioxidant neuroprotection in Alzheimer's disease as preventive and therapeutic approach,” Free Radical Biology and Medicine, vol. 33, no. 2, pp. 182–191, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. G. D. Zeevalk, L. Manzino, P. K. Sonsalla, and L. P. Bernard, “Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease,” Experimental Neurology, vol. 203, no. 2, pp. 512–520, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. I. Cacciatore, C. Cornacchia, F. Pinnen, A. Mollica, and A. di Stefano, “Prodrug approach for increasing cellular glutathione levels,” Molecules, vol. 15, no. 3, pp. 1242–1264, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. I. Cacciatore, A. Cocco, M. Costa et al., “Biochemical properties of new synthetic carnosine analogues containing the residue of 2,3-diaminopropionic acid: the effect of N-acetylation,” Amino Acids, vol. 28, no. 1, pp. 77–83, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. L. Brunetti, I. Cacciatore, A. di Stefano et al., “Synthesis and biological evaluation of a novel pyroglutamyl-modified TRH analogue,” Farmaco, vol. 57, no. 6, pp. 479–486, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. N. Denora, A. Trapani, V. Laquintana, A. Lopedota, and G. Trapani, “Recent advances in medicinal chemistry and pharmaceutical technology-strategies for drug delivery to the brain,” Current Topics in Medicinal Chemistry, vol. 9, no. 2, pp. 182–196, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. I. Cacciatore, A. di Stefano, G. Luisi, F. Pinnen, and P. Sozio, “Transition state isosteres of the γ-glutamyl peptide bond hydrolysis: synthesis and characterization of the ψ (CH2NH) pseudopeptide analogue of glutathione,” Journal of Peptide Science, vol. 10, no. 2, pp. 109–114, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. I. Cacciatore, A. M. Caccuri, A. di Stefano et al., “Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage,” Farmaco, vol. 58, no. 9, pp. 787–793, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. I. Cacciatore, A. M. Caccuri, A. Cocco et al., “Potent isozyme-selective inhibition of human glutathione S-transferase A1-1 by a novel glutathione S-conjugate,” Amino Acids, vol. 29, no. 3, pp. 255–261, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. N. Das, M. Dhanawat, B. Dash, R. C. Nagarwal, and S. K. Shrivastava, “Codrug: an efficient approach for drug optimization,” European Journal of Pharmaceutical Sciences, vol. 41, no. 5, pp. 571–588, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Decker, “Hybrid molecules incorporating natural products: applications in cancer therapy, neurodegenerative disorders and beyond,” Current Medicinal Chemistry, vol. 18, no. 10, pp. 1464–1475, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Minelli, C. Conte, I. Cacciatore, C. Cornacchia, and F. Pinnen, “Molecular mechanism underlying the cerebral effect of Gly-Pro-Glu tripeptide bound to L-dopa in a Parkinson's animal model,” Amino Acids. In press. View at Publisher · View at Google Scholar
  66. P. Sozio, A. Iannitelli, L. S. Cerasa et al., “New L-dopa codrugs as potential antiparkinson agents,” Archiv der Pharmazie, vol. 341, no. 7, pp. 412–417, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Malakoutikhah, M. Teixidó, and E. Giralt, “Toward an optimal blood-brain barrier shuttle by synthesis and evaluation of peptide libraries,” Journal of Medicinal Chemistry, vol. 51, no. 16, pp. 4881–4889, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. R. Kannan, J. F. Kuhlenkamp, E. Jeandidier, H. Trinh, M. Ookhtens, and N. Kaplowitz, “Evidence for carrier-mediated transport of glutathione across the blood-brain barrier in the rat,” Journal of Clinical Investigation, vol. 85, no. 6, pp. 2009–2013, 1990. View at Scopus
  69. F. Pinnen, I. Cacciatore, C. Cornacchia et al., “Synthesis and study of L-dopa-glutathione codrugs as new anti-Parkinson agents with free radical scavenging properties,” Journal of Medicinal Chemistry, vol. 50, no. 10, pp. 2506–2515, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. S. S. More and R. Vince, “Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugs,” Journal of Medicinal Chemistry, vol. 51, no. 15, pp. 4581–4588, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. U. Bickel, Y. S. Kang, and W. M. Pardridge, “In vivo cleavability of a disulfide-based chimeric opioid peptide in rat brain,” Bioconjugate Chemistry, vol. 6, no. 2, pp. 211–218, 1995. View at Scopus
  72. F. Pinnen, I. Cacciatore, C. Cornacchia et al., “CNS delivery of l-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug,” Amino Acids, vol. 42, no. 1, pp. 261–269, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. K. Ehrlich, S. Viirlaid, R. Mahlapuu et al., “Design, synthesis and properties of novel powerful antioxidants, glutathione analogues,” Free Radical Research, vol. 41, no. 7, pp. 779–787, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Ehrlich, K. Ida, R. Mahlapuu et al., “Characterization of UPF peptides, members of the glutathione analogues library, on the basis of their effects on oxidative stress-related enzymes,” Free Radical Research, vol. 43, no. 6, pp. 572–580, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Põder, M. Zilmer, J. Starkopf et al., “An antioxidant tetrapeptide UPF1 in rats has a neuroprotective effect in transient global brain ischemia,” Neuroscience Letters, vol. 370, no. 1, pp. 45–50, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. E. Karelson, R. Mahlapuu, M. Zilmer, U. Soomets, N. Bogdanovic, and Ü Langel, “Possible signaling by glutathione and its novel analogue through potent stimulation of frontocortical G proteins in normal aging and in Alzheimer's disease,” Annals of the New York Academy of Sciences, vol. 973, pp. 537–540, 2002. View at Scopus
  77. F. Pinnen, P. Sozio, I. Cacciatore et al., “Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease,” Archiv der Pharmazie, vol. 344, no. 3, pp. 139–148, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. K. N. Prasad, W. C. Cole, and K. C. Prasad, “Risk factors for Alzheimer's disease: role of multiple antioxidants, non-steroidal anti-inflammatory and cholinergic agents alone or in combination in prevention and treatment,” Journal of the American College of Nutrition, vol. 21, no. 6, pp. 506–522, 2002. View at Scopus
  79. G. P. Lim, F. Yang, T. Chu et al., “Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease,” Journal of Neuroscience, vol. 20, no. 15, pp. 5709–5714, 2000. View at Scopus
  80. Q. Yan, J. Zhang, H. Liu et al., “Anti-inflammatory drug therapy alters β-amyloid processing and deposition in an animal model of Alzheimer's disease,” Journal of Neuroscience, vol. 23, no. 20, pp. 7504–7509, 2003. View at Scopus
  81. G. Atmaca, “Antioxidant effects of sulfur-containing amino acids,” Yonsei Medical Journal, vol. 45, no. 5, pp. 776–788, 2004. View at Scopus
  82. F. Pinnen, I. Cacciatore, C. Cornacchia et al., “Codrugs linking L-dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson's disease,” Journal of Medicinal Chemistry, vol. 52, no. 2, pp. 559–563, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. D. Offen, I. Ziv, H. Sternin, E. Melamed, and A. Hochman, “Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease,” Experimental Neurology, vol. 141, no. 1, pp. 32–39, 1996. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Minelli, C. Conte, E. Prudenzi et al., “N-Acetyl-L-Methionyl-L-Dopa-Methyl Ester as a dual acting drug that relieves L-Dopa-induced oxidative toxicity,” Free Radical Biology and Medicine, vol. 49, no. 1, pp. 31–39, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. J. L. Torres, C. Lozano, and P. Maher, “Conjugation of catechins with cysteine generates antioxidant compounds with enhanced neuroprotective activity,” Phytochemistry, vol. 66, no. 17, pp. 2032–2037, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. P. Maher, J. Lewerenz, C. Lozano, and J. L. Torres, “A novel approach to enhancing cellular glutathione levels,” Journal of Neurochemistry, vol. 107, no. 3, pp. 690–700, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. H. Sato, M. Tamba, T. Ishii, and S. Bannai, “Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins,” Journal of Biological Chemistry, vol. 274, no. 17, pp. 11455–11458, 1999. View at Publisher · View at Google Scholar · View at Scopus
  88. S. R. Steinhubl, “Why have antioxidants failed in clinical trials?” American Journal of Cardiology, vol. 101, supplement 10, pp. S14–S19, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. D. V. Ratnam, D. D. Ankola, V. Bhardwaj, D. K. Sahana, and M. N. V. R. Kumar, “Role of antioxidants in prophylaxis and therapy: a pharmaceutical perspective,” Journal of Controlled Release, vol. 113, no. 3, pp. 189–207, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. J. L. Gilmore, X. Yi, L. Quan, and A. V. Kabanov, “Novel nanomaterials for clinical neuroscience,” Journal of NeuroImmune Pharmacology, vol. 3, no. 2, pp. 83–94, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. C. Chen, D. Han, C. Cai, and X. Tang, “An overview of liposome lyophilization and its future potential,” Journal of Controlled Release, vol. 142, no. 3, pp. 299–311, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. G. D. Zeevalk, L. P. Bernard, and F. T. Guilford, “Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells,” Neurochemical Research, vol. 35, no. 10, pp. 1575–1587, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. W. H. de Jong and P. J. A. Borm, “Drug delivery and nanoparticles: applications and hazards,” International Journal of Nanomedicine, vol. 3, no. 2, pp. 133–149, 2008. View at Scopus
  94. A. Aumelas, A. Serrero, A. Durand, E. Dellacherie, and M. Leonard, “Nanoparticles of hydrophobically modified dextrans as potential drug carrier systems,” Colloids and Surfaces B, vol. 59, no. 1, pp. 74–80, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. F. Esmaeili, M. H. Ghahremani, B. Esmaeili, M. R. Khoshayand, F. Atyabi, and R. Dinarvand, “PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution,” International Journal of Pharmaceutics, vol. 349, no. 1-2, pp. 249–255, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. S. R. Williams, B. S. Lepene, C. D. Thatcher, and T. E. Long, “Synthesis and characterization of poly(ethylene glycol)-glutathione conjugate self-assembled nanoparticles for antioxidant delivery,” Biomacromolecules, vol. 10, no. 1, pp. 155–161, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. N. A. Alcantar, E. S. Aydil, and J. N. Israelachvili, “Polyethylene glycol-coated biocompatible surfaces,” Journal of Biomedical Materials Research, vol. 51, no. 3, pp. 343–351, 2000.
  98. S. H. Koo, J. S. Lee, G. H. Kim, and H. G. Lee, “Preparation, characteristics, and stability of glutathione-loaded nanoparticles,” Journal of Agricultural and Food Chemistry, vol. 9, pp. 11264–11269, 2011.
  99. S. A. Agnihotri, N. N. Mallikarjuna, and T. M. Aminabhavi, “Recent advances on chitosan-based micro- and nanoparticles in drug delivery,” Journal of Controlled Release, vol. 100, no. 1, pp. 5–28, 2004. View at Publisher · View at Google Scholar · View at Scopus
  100. H. Takeuchi, H. Yamamoto, and Y. Kawashima, “Mucoadhesive nanoparticulate systems for peptide drug delivery,” Advanced Drug Delivery Reviews, vol. 47, no. 1, pp. 39–54, 2001. View at Publisher · View at Google Scholar · View at Scopus