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Hepatoprotective Effect of Trehalose: Insight into Its Mechanisms of Action

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Natural Products and Human Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 1328))

Abstract

Trehalose is a nonreducing disaccharide formed by two glucose molecules. It has been shown that trehalose can protect proteins and cellular membranes against the adverse effects of different types of stress, such as dehydration, cold, heat, and oxidation. Chronic liver disease has emerged as an important cause of morbidity and mortality throughout the world. This disaccharide has received attention for its hepatoprotective activities against liver damage. The main mechanisms underlying the hepatoprotective action of trehalose are reducing inflammatory signaling, enhancing antioxidant defense, and induction of autophagy.

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References

  1. Elbein, A. D., Pan, Y., Pastuszak, I., & Carroll, D. (2003). New insights on trehalose: A multifunctional molecule. Glycobiology, 13(4), 17R–27R.

    Article  CAS  PubMed  Google Scholar 

  2. Iturriaga, G., Suárez, R., & Nova-Franco, B. (2009). Trehalose metabolism: From osmoprotection to signaling. International Journal of Molecular Sciences, 10(9), 3793–3810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Luyckx, J., & Baudouin, C. (2011). Trehalose: An intriguing disaccharide with potential for medical application in ophthalmology. Clinical Ophthalmology (Auckland, NZ), 5, 577.

    CAS  Google Scholar 

  4. Argüelles, J.-C. (2014). Why can’t vertebrates synthesize trehalose? Journal of Molecular Evolution, 79(3–4), 111–116.

    Article  PubMed  Google Scholar 

  5. Crowe, J. H., Tablin, F., Wolkers, W. F., Gousset, K., Tsvetkova, N. M., & Ricker, J. (2003). Stabilization of membranes in human platelets freeze-dried with trehalose. Chemistry and Physics of Lipids, 122(1), 41–52.

    Article  CAS  PubMed  Google Scholar 

  6. Singer, M. A., & Lindquist, S. (1998). Multiple effects of trehalose on protein folding in vitro and in vivo. Molecular Cell, 1(5), 639–648.

    Article  CAS  PubMed  Google Scholar 

  7. Khalifeh, M., Barreto, G. E., Sahebkar, A. (2021). Therapeutic potential of trehalose in neurodegenerative diseases: The knowns and unknowns. Neural Regeneration Research, 16(10), 2026–2027.

    Google Scholar 

  8. Khalifeh, M., Read, M. I., Barreto, G. E., Sahebkar, A. (2020). Trehalose against Alzheimer’s Disease: Insights into a Potential Therapy. Bioessays, 42(8), e1900195.

    Google Scholar 

  9. Yaribeygi, H., Yaribeygi, A., Sathyapalan, T., Sahebkar, A. (2019). Molecular mechanisms of trehalose in modulating glucose homeostasis in diabetes. Diabetes & Metabolic Syndrome, 13(3), 2214–2218.

    Google Scholar 

  10. Khalifeh, M., Barreto, G. E., Sahebkar, A. (2019). Trehalose as a promising therapeutic candidate for the treatment of Parkinson’s disease. British Journal of Pharmacology, 176(9), 1173–1189.

    Google Scholar 

  11. Sahebkar, A., Hatamipour, M., Tabatabaei, S. A. (2019). Trehalose administration attenuates atherosclerosis in rabbits fed a high-fat diet. Journal of Cellular Biochemistry, 120(6), 9455–9459.

    Google Scholar 

  12. Rodríguez-Navarro, J. A., Rodríguez, L., Casarejos, M. J., Solano, R. M., Gómez, A., Perucho, J., et al. (2010). Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neurobiology of Disease, 39(3), 423–438.

    Article  PubMed  Google Scholar 

  13. Echigo, R., Shimohata, N., Karatsu, K., Yano, F., Kayasuga-Kariya, Y., Fujisawa, A., et al. (2012). Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage. Journal of Translational Medicine, 10(1), 80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tanji, K., Miki, Y., Maruyama, A., Mimura, J., Matsumiya, T., Mori, F., et al. (2015). Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease. Biochemical and Biophysical Research Communications, 465(4), 746–752.

    Article  CAS  PubMed  Google Scholar 

  15. Tanaka, M., Machida, Y., Niu, S., Ikeda, T., Jana, N. R., Doi, H., et al. (2004). Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nature Medicine, 10(2), 148.

    Article  CAS  PubMed  Google Scholar 

  16. Castillo, K., Nassif, M., Valenzuela, V., Rojas, F., Matus, S., Mercado, G., et al. (2013). Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy, 9(9), 1308–1320.

    Article  CAS  PubMed  Google Scholar 

  17. Holler, C. J., Taylor, G., McEachin, Z. T., Deng, Q., Watkins, W. J., Hudson, K., et al. (2016). Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: A novel therapeutic lead to treat frontotemporal dementia. Molecular Neurodegeneration, 11(1), 46.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Pagliassotti, M. J., Estrada, A. L., Hudson, W. M., Wei, Y., Wang, D., Seals, D. R., et al. (2017). Trehalose supplementation reduces hepatic endoplasmic reticulum stress and inflammatory signaling in old mice. The Journal of Nutritional Biochemistry, 45, 15–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. DeBosch, B. J., Heitmeier, M. R., Mayer, A. L., Higgins, C. B., Crowley, J. R., Kraft, T. E., et al. (2016). Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis. Science Signaling, 9(416), ra21–ra21.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Minutoli, L., Altavilla, D., Bitto, A., Polito, F., Bellocco, E., Laganà, G., et al. (2008). Trehalose: A biophysics approach to modulate the inflammatory response during endotoxic shock. European Journal of Pharmacology, 589(1), 272–280.

    Article  CAS  PubMed  Google Scholar 

  21. Taub, R. (2004). Liver regeneration: From myth to mechanism. Nature Reviews Molecular Cell Biology, 5(10), 836.

    Article  CAS  PubMed  Google Scholar 

  22. Farkhondeh, T., & Samarghandian, S. (2016). The hepatoprotective effects of curcumin against drugs and toxic agents: An updated review. Toxin Reviews, 35(3–4), 133–140.

    Article  CAS  Google Scholar 

  23. Taghikhani, A., Ansari Samani, R., Afrogh, H., Fard, S., Ganji, F., Asgari, A., et al. (2012). The hepatotoxic effects of stachys Lavandulifolia vahl on wistar rat. Journal of Mazandaran University of Medical Sciences, 22(88), 81–87.

    Google Scholar 

  24. Samarghandian, S., Azimi-Nezhad, M., Afshari, R., Farkhondeh, T., & Karimnezhad, F. (2015). Effects of buprenorphine on balance of oxidant/antioxidant system in the different ages of male rat liver. Journal of Biochemical and Molecular Toxicology, 29(6), 249–253.

    Article  CAS  PubMed  Google Scholar 

  25. Lim, Y.-S., & Kim, W. R. (2008). The global impact of hepatic fibrosis and end-stage liver disease. Clinics in Liver Disease, 12(4), 733–746.

    Article  PubMed  Google Scholar 

  26. Wong, R. J., Aguilar, M., Cheung, R., Perumpail, R. B., Harrison, S. A., Younossi, Z. M., et al. (2015). Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology, 148(3), 547–555.

    Article  PubMed  Google Scholar 

  27. Lin, S.-Y., Wang, Y.-Y., Chen, W.-Y., Liao, S.-L., Chou, S.-T., Yang, C.-P., et al. (2017). Hepatoprotective activities of rosmarinic acid against extrahepatic cholestasis in rats. Food and Chemical Toxicology, 108, 214–223.

    Article  CAS  PubMed  Google Scholar 

  28. Schuppan, D., & Afdhal, N. H. (2008). Liver cirrhosis. The Lancet, 371(9615), 838–851.

    Article  CAS  Google Scholar 

  29. Ichai, P., & Samuel, D. (2008). Etiology and prognosis of fulminant hepatitis in adults. Liver Transplantation, 14(S2), S67–S79.

    Article  PubMed  Google Scholar 

  30. Bhatia, V., Singhal, A., Panda, S. K., & Acharya, S. K. (2008). A 20-year single-center experience with acute liver failure during pregnancy: Is the prognosis really worse? Hepatology, 48(5), 1577–1585.

    Article  PubMed  Google Scholar 

  31. Liu, R., Zhao, R., Zhou, X., Liang, X., Campbell, D. J., Zhang, X., et al. (2014). Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2. Hepatology, 60(3), 908–918.

    Article  CAS  PubMed  Google Scholar 

  32. Tajiri, K., & Shimizu, Y. (2017). Recent advances in the management of pruritus in chronic liver diseases. World Journal of Gastroenterology, 23(19), 3418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kremer, A. E., van Dijk, R., Leckie, P., Schaap, F. G., Kuiper, E. M., Mettang, T., et al. (2012). Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology, 56(4), 1391–1400.

    Article  CAS  PubMed  Google Scholar 

  34. Jüngst, C., & Lammert, F. (2013). Cholestatic liver disease. Digestive Diseases, 31(1), 152–154.

    Article  PubMed  Google Scholar 

  35. Wasley, A., Fiore, A., & Bell, B. P. (2006). Hepatitis A in the era of vaccination. Epidemiologic Reviews, 28(1), 101–111.

    Article  PubMed  Google Scholar 

  36. Bernal, W., Auzinger, G., Dhawan, A., & Wendon, J. (2010). Acute liver failure. The Lancet, 376(9736), 190–201.

    Article  Google Scholar 

  37. Guarino, M., Tosoni, A., & Nebuloni, M. (2009). Direct contribution of epithelium to organ fibrosis: Epithelial-mesenchymal transition. Human Pathology, 40(10), 1365–1376.

    Article  CAS  PubMed  Google Scholar 

  38. Wynn, T. (2008). Cellular and molecular mechanisms of fibrosis. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland, 214(2), 199–210.

    Article  CAS  Google Scholar 

  39. Leask, A., & Abraham, D. J. (2004). TGF-β signaling and the fibrotic response. The FASEB Journal, 18(7), 816–827.

    Article  CAS  PubMed  Google Scholar 

  40. Li, G.-S., Jiang, W.-L., Tian, J.-W., Qu, G.-W., Zhu, H.-B., & Fu, F.-H. (2010). In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis. Phytomedicine, 17(3–4), 282–288.

    Article  CAS  PubMed  Google Scholar 

  41. Robinson, M. W., Harmon, C., & O’Farrelly, C. (2016). Liver immunology and its role in inflammation and homeostasis. Cellular & Molecular Immunology, 13(3), 267.

    Article  CAS  Google Scholar 

  42. Bruha, R., Dvorak, K., & Petrtyl, J. (2012). Alcoholic liver disease. World Journal of Hepatology, 4(3), 81.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yin, M., Wheeler, M. D., Kono, H., Bradford, B. U., Gallucci, R. M., Luster, M. I., et al. (1999). Essential role of tumor necrosis factor α in alcohol-induced liver injury in mice. Gastroenterology, 117(4), 942–952.

    Article  CAS  PubMed  Google Scholar 

  44. Donohue, T. M., Jr. (2007). Alcohol-induced steatosis in liver cells. World Journal of Gastroenterology: WJG, 13(37), 4974.

    Article  CAS  PubMed  Google Scholar 

  45. Bhattacharya, R., & Shuhart, M. C. (2003). Hepatitis C and alcohol: Interactions, outcomes, and implications. Journal of Clinical Gastroenterology, 36(3), 242–252.

    Article  PubMed  Google Scholar 

  46. Naveau, S., Giraud, V., Borotto, E., Aubert, A., Capron, F., & Chaput, J. (1997). Excess weight risk factor for alcoholic liver disease. Hepatology, 25(1), 108–111.

    Article  CAS  PubMed  Google Scholar 

  47. Fujii, H., & Kawada, N. (2014). Fibrogenesis in alcoholic liver disease. World Journal of Gastroenterology: WJG, 20(25), 8048.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Oishi, N., Yamashita, T., & Kaneko, S. (2014). Molecular biology of liver cancer stem cells. Liver Cancer, 3(2), 71–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rantala, M., & Van de Laar, M. (2008). Surveillance and epidemiology of hepatitis B and C in Europe – A review. Eurosurveillance, 13(21), 18880.

    Article  PubMed  Google Scholar 

  50. Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: Back to Virchow? The Lancet, 357(9255), 539–545.

    Article  CAS  Google Scholar 

  51. Karin, M., & Greten, F. R. (2005). NF-κB: Linking inflammation and immunity to cancer development and progression. Nature Reviews Immunology, 5(10), 749.

    Article  CAS  PubMed  Google Scholar 

  52. Sakurai, T., Maeda, S., Chang, L., & Karin, M. (2006). Loss of hepatic NF-κB activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proceedings of the National Academy of Sciences, 103(28), 10544–10551.

    Article  CAS  Google Scholar 

  53. He, G., & Karin, M. (2011). NF-κB and STAT3 – Key players in liver inflammation and cancer. Cell Research, 21(1), 159.

    Article  CAS  PubMed  Google Scholar 

  54. Asadi-Samani, M., Kafash-Farkhad, N., Azimi, N., Fasihi, A., Alinia-Ahandani, E., & Rafieian-Kopaei, M. (2015). Medicinal plants with hepatoprotective activity in Iranian folk medicine. Asian Pacific Journal of Tropical Biomedicine, 5(2), 146–157.

    Article  CAS  Google Scholar 

  55. Louvet, A., & Mathurin, P. (2015). Alcoholic liver disease: Mechanisms of injury and targeted treatment. Nature Reviews Gastroenterology & Hepatology, 12(4), 231.

    Article  Google Scholar 

  56. Mitry, R. R., Hughes, R. D., & Dhawan, A. (2002). Progress in human hepatocytes: Isolation, culture & cryopreservation. In Seminars in cell & developmental biology (Vol. 13, pp. 463–467). New York: Elsevier.

    Google Scholar 

  57. Cardoso, L., Pinto, M. A., Henriques Pons, A., & Alves, L. A. (2017). Cryopreservation of rat hepatocytes with disaccharides for cell therapy. Cryobiology, 78, 15–21.

    Article  CAS  PubMed  Google Scholar 

  58. Illouz, S., Nakamura, T., Webb, M., Thava, B., Bikchandani, J., Robertson, G., et al. (2008). Comparison of University of Wisconsin and ET-Kyoto preservation solutions for the cryopreservation of primary human hepatocytes. Transplantation Proceedings, 40(5), 1706–1709.

    Article  CAS  PubMed  Google Scholar 

  59. Katenz, E., Vondran, F. W., Schwartlander, R., Pless, G., Gong, X., Cheng, X., et al. (2007). Cryopreservation of primary human hepatocytes: The benefit of trehalose as an additional cryoprotective agent. Liver Transplantation, 13(1), 38–45.

    Article  PubMed  Google Scholar 

  60. Stokich, B., Osgood, Q., Grimm, D., Moorthy, S., Chakraborty, N., & Menze, M. A. (2014). Cryopreservation of hepatocyte (HepG2) cell monolayers: Impact of trehalose. Cryobiology, 69(2), 281–290.

    Article  CAS  PubMed  Google Scholar 

  61. Jiang, L., Shen, C., Dai, J., & Meng, Q. (2013). Di-rhamnolipids improve effect of trehalose on both hypothermic preservation and cryopreservation of rat hepatocytes. Applied Microbiology and Biotechnology, 97(10), 4553–4561.

    Article  CAS  PubMed  Google Scholar 

  62. Honma, Y., Sato-Morita, M., Katsuki, Y., Mihara, H., Baba, R., & Harada, M. (2018). Trehalose activates autophagy and decreases proteasome inhibitor-induced endoplasmic reticulum stress and oxidative stress-mediated cytotoxicity in hepatocytes. Hepatology Research, 48(1), 94–105.

    Article  CAS  PubMed  Google Scholar 

  63. Leekumjorn, S., Wu, Y., Sum, A. K., & Chan, C. (2008). Experimental and computational studies investigating trehalose protection of HepG2 cells from palmitate-induced toxicity. Biophysical Journal, 94(7), 2869–2883.

    Article  CAS  PubMed  Google Scholar 

  64. Matsumoto, Y., Cao, E., & Ueoka, R. (2013). Growth inhibition by novel liposomes including trehalose surfactant against hepatocarcinoma cells along with apoptosis. Anticancer Research, 33(11), 4727–4740.

    CAS  PubMed  Google Scholar 

  65. Mukorah, F., Razunguzwa, B., & Masola, B. (1998). Stabilization of rat liver mitochondrial alanine aminotransferase with ethanol and trehalose. Cryobiology, 37(4), 300–308.

    Article  CAS  PubMed  Google Scholar 

  66. Mayer, A. L., Higgins, C. B., Heitmeier, M. R., Kraft, T. E., Qian, X., Crowley, J. R., et al. (2016). SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy. Scientific Reports, 6, 38586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Liu, X.-H., Aksan, A., Menze, M. A., Hand, S. C., & Toner, M. (2005). Trehalose loading through the mitochondrial permeability transition pore enhances desiccation tolerance in rat liver mitochondria. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1717(1), 21–26.

    Article  CAS  Google Scholar 

  68. Gong, Z.-G., Wang, X.-Y., Wang, J.-H., Fan, R.-F., & Wang, L. (2019). Trehalose prevents cadmium-induced hepatotoxicity by blocking Nrf2 pathway, restoring autophagy and inhibiting apoptosis. Journal of Inorganic Biochemistry, 192, 62–71.

    Article  CAS  PubMed  Google Scholar 

  69. Qu, K.-C., Wang, Z.-Y., Tang, K.-K., Zhu, Y.-S., & Fan, R.-F. (2019). Trehalose suppresses cadmium-activated Nrf2 signaling pathway to protect against spleen injury. Ecotoxicology and Environmental Safety, 181, 224–230.

    Article  CAS  PubMed  Google Scholar 

  70. Zhang, Y., Higgins, C. B., Mayer, A. L., Mysorekar, I. U., Razani, B., Graham, M. J., et al. (2018). TFEB-dependent induction of thermogenesis by the hepatocyte SLC2A inhibitor trehalose. Autophagy, 14(11), 1959–1975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Stachowicz, A., Wiśniewska, A., Kuś, K., Kiepura, A., Gębska, A., Gajda, M., et al. (2019). The influence of trehalose on atherosclerosis and hepatic steatosis in apolipoprotein E knockout mice. International Journal of Molecular Sciences, 20(7), 1552.

    Article  CAS  PubMed Central  Google Scholar 

  72. Ciancarelli, I., De Amicis, D., Di Massimo, C., Carolei, A., & Giuliana Tozzi Ciancarelli, M. (2012). Oxidative stress in post-acute ischemic stroke patients after intensive neurorehabilitation. Current Neurovascular Research, 9(4), 266–273.

    Article  CAS  PubMed  Google Scholar 

  73. Lukic-Panin, V., Deguchi, K., Yamashita, T., Shang, J., Zhang, X., Tian, F., et al. (2010). Free radical scavenger edaravone administration protects against tissue plasminogen activator induced oxidative stress and blood brain barrier damage. Current Neurovascular Research, 7(4), 319–329.

    Article  CAS  PubMed  Google Scholar 

  74. Herdeiro, R., Pereira, M., Panek, A., & Eleutherio, E. (2006). Trehalose protects Saccharomyces cerevisiae from lipid peroxidation during oxidative stress. Biochimica et Biophysica Acta (BBA)-General Subjects, 1760(3), 340–346.

    Article  CAS  Google Scholar 

  75. Oku, K., Watanabe, H., Kubota, M., Fukuda, S., Kurimoto, M., Tsujisaka, Y., et al. (2003). NMR and quantum chemical study on the OḤ··π and CḤ··O interactions between trehalose and unsaturated fatty acids: Implication for the mechanism of antioxidant function of trehalose. Journal of the American Chemical Society, 125(42), 12739–12748.

    Google Scholar 

  76. Yang, B., Bai, Y., Yin, C., Qian, H., **ng, G., Wang, S., et al. (2018). Activation of autophagic flux and the Nrf2/ARE signaling pathway by hydrogen sulfide protects against acrylonitrile-induced neurotoxicity in primary rat astrocytes. Archives of Toxicology, 92(6), 2093–2108.

    Article  CAS  PubMed  Google Scholar 

  77. Montes, S., Juárez-Rebollar, D., Nava-Ruíz, C., Sánchez-García, A., Heras-Romero, Y., Rios, C., et al. (2015). Immunohistochemical study of Nrf2-antioxidant response element as indicator of oxidative stress induced by cadmium in develo** rats. Oxidative Medicine and Cellular Longevity, 2015, 1–9.

    Article  Google Scholar 

  78. Ugun-Klusek, A., Tatham, M. H., Elkharaz, J., Constantin-Teodosiu, D., Lawler, K., Mohamed, H., et al. (2017). Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway. Cell Death & Disease, 8(1), e2531.

    Article  CAS  Google Scholar 

  79. Thellung, S., Scoti, B., Corsaro, A., Villa, V., Nizzari, M., Gagliani, M. C., et al. (2018). Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death. Cell Death & Disease, 9(2), 166.

    Article  Google Scholar 

  80. He, Y., Li, S., Zhang, W., Dai, W., Cui, T., Wang, G., et al. (2017). Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo. Scientific Reports, 7, 42394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bellezza, I., Giambanco, I., Minelli, A., & Donato, R. (2018). Nrf2-Keap1 signaling in oxidative and reductive stress. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1865(5), 721–733.

    Article  CAS  Google Scholar 

  82. Jiang, P., & Mizushima, N. (2015). LC3-and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells. Methods, 75, 13–18.

    Article  CAS  PubMed  Google Scholar 

  83. Sarkar, S., Davies, J. E., Huang, Z., Tunnacliffe, A., & Rubinsztein, D. C. (2007). Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and α-synuclein. Journal of Biological Chemistry, 282(8), 5641–5652.

    Article  CAS  PubMed  Google Scholar 

  84. Matsunaga, K., Saitoh, T., Tabata, K., Omori, H., Satoh, T., Kurotori, N., et al. (2009). Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nature Cell Biology, 11(4), 385.

    Article  CAS  PubMed  Google Scholar 

  85. Wirawan, E., Lippens, S., Vanden Berghe, T., Romagnoli, A., Fimia, G. M., Piacentini, M., et al. (2012). Beclin1: A role in membrane dynamics and beyond. Autophagy, 8(1), 6–17.

    Article  CAS  PubMed  Google Scholar 

  86. Lim, J. P., & Gleeson, P. A. (2011). Macropinocytosis: An endocytic pathway for internalising large gulps. Immunology and Cell Biology, 89(8), 836.

    Article  CAS  PubMed  Google Scholar 

  87. Deng, D., Xu, C., Sun, P., Wu, J., Yan, C., Hu, M., et al. (2014). Crystal structure of the human glucose transporter GLUT1. Nature, 510(7503), 121.

    Article  CAS  PubMed  Google Scholar 

  88. Mayer, A. L., Higgins, C. B., Heitmeier, M. R., Kraft, T. E., Qian, X., Crowley, J. R., et al. (2016). SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy. Scientific Reports, 63, 8586.

    Google Scholar 

  89. Youm, Y.-H., Grant, R. W., McCabe, L. R., Albarado, D. C., Nguyen, K. Y., Ravussin, A., et al. (2013). Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metabolism, 18(4), 519–532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Szabo, G., & Csak, T. (2012). Inflammasomes in liver diseases. Journal of Hepatology, 57(3), 642–654.

    Article  CAS  PubMed  Google Scholar 

  91. Hotamisligil, G. S. (2010). Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell, 140(6), 900–917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Rutkowski, D. T., & Hegde, R. S. (2010). Regulation of basal cellular physiology by the homeostatic unfolded protein response. The Journal of Cell Biology, 189(5), 783–794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hosseinpour-Moghaddam, K., Caraglia, M., & Sahebkar, A. (2018). Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts. Journal of Cellular Physiology, 233(9), 6524–6543.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar

  2. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

    Paul C. Guest

  3. Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran

    Tannaz Jamialahmadi

  4. Faculty of Medicine, Department of Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran

    Tannaz Jamialahmadi

  5. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  6. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  7. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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  1. Fatemeh Forouzanfar
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  2. Paul C. Guest
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  3. Tannaz Jamialahmadi
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  4. Amirhossein Sahebkar
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Correspondence to Amirhossein Sahebkar .

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  1. Pharmacy, Medical Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  2. Diabetes, Endocrinology & Metabolism, The University of Hull, Brough, UK

    Thozhukat Sathyapalan

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Forouzanfar, F., Guest, P.C., Jamialahmadi, T., Sahebkar, A. (2021). Hepatoprotective Effect of Trehalose: Insight into Its Mechanisms of Action. In: Sahebkar, A., Sathyapalan, T. (eds) Natural Products and Human Diseases. Advances in Experimental Medicine and Biology(), vol 1328. Springer, Cham. https://doi.org/10.1007/978-3-030-73234-9_34

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