Metal ion effects on Aβ and tau aggregation

International Journal of Molecular Sciences

Volumn 19, Issue 1, 2018, Pages

  Kim, Anne Claire ^a,b   Lim, Sungsu ^b   Kim, Yun Kyung ^b  

^a WELLESLEY COLLEGE   (United States)

^b Korea Institute of Science and Technology   (South Korea)

Author keywords

Metal; Tau; amyloid

Indexed keywords

ALPHA SECRETASE; ALUMINUM; AMYLOID BETA PROTEIN; BETA SECRETASE; CADMIUM; COPPER; CYCLIN DEPENDENT KINASE 5; GAMMA SECRETASE; GLYCOGEN SYNTHASE KINASE 3BETA; IRON; LEAD; LITHIUM; MAGNESIUM; MANGANESE; MEMBRANE PROTEIN; MERCURY; METAL ION; PHOSPHATASE LIKE PROTEIN PHOSPHATASE 2A; PROTEIN P25; TAU PROTEIN; UNCLASSIFIED DRUG; ZINC; ION; METAL; PROTEIN AGGREGATE;

AGING; ALZHEIMER DISEASE; ENVIRONMENTAL EXPOSURE; ENZYME ACTIVITY; HOMEOSTASIS; HUMAN; MOLECULAR PATHOLOGY; NEUROTOXICITY; NONHUMAN; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; DRUG EFFECT; ENVIRONMENT; METABOLISM;

AMYLOID BETA-PEPTIDES; ENVIRONMENT; HUMANS; IONS; METALS; PROTEIN AGGREGATES; TAU PROTEINS;

EID: 85040035859     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms19010128     Document Type: Review

References (100)

1. Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2017, 13, 325-373.
2. Niccoli, T., Partridge, L. Ageing as a risk factor for disease. Curr. Biol. 2012, 22, R741-R752.
3. Waldron, K.J., Rutherford, J.C., Ford, D., Robinson, N.J. Metalloproteins and metal sensing. Nature 2009, 460, 823-830.
4. Banci, L., Bertini, I. Metallomics and the Cell, Springer: Basel, Switzerland, 2013.
5. Myhre, O., Utkilen, H., Duale, N., Brunborg, G., Hofer, T. Metal dyshomeostasis and inflammation in Alzheimer’s and Parkinson’s diseases: Possible impact of environmental exposures. Oxid. Med. Cell. Longev. 2013, 2013, doi:10.1155/2013/726954.
6. Wright, R.O., Baccarelli, A. Metals and neurotoxicology. J. Nutr. 2007, 137, 2809-2813.
7. Bush, A.I. The metal theory of Alzheimer’s disease. J. Alzheimer’s Dis. 2013, 33, S277-S281.
8. Tchounwou, P.B., Yedjou, C.G., Patlolla, A.K., Sutton, D.J. Heavy metal toxicity and the environment. In Molecular, Clinical and Environmental Toxicology, Springer: Basel, Switzerland, 2012, pp. 133-164.
9. Bloom, G.S. Amyloid-β and tau: The trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014, 71, 505-508.
10. Hardy, J.A., Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science 1992, 256, 184-185.
11. Kolarova, M., García-Sierra, F., Bartos, A., Ricny, J., Ripova, D. Structure and pathology of tau protein in Alzheimer disease. Int. J. Alzheimer’s Dis. 2012, 2012, doi:10.1155/2012/731526.
12. Gómez-Isla, T., Hollister, R., West, H., Mui, S., Growdon, J.H., Petersen, R.C., Parisi, J.E., Hyman, B.T. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann. Neurol. 1997, 41, 17-24.
13. O’Brien, R.J., Wong, P.C. Amyloid precursor protein processing and Alzheimer’s disease. Annu. Rev. Neurosci. 2011, 34, 185-204.
14. Kimura, T., Ishiguro, K., Hisanaga, S.-I. Physiological and pathological phosphorylation of tau by cdk5. Front. Mol. Neurosci. 2014, 7, doi:10.3389/fnmol.2014.00065.
15. Rankin, C.A., Sun, Q., Gamblin, T.C. Tau phosphorylation by gsk-3β promotes tangle-like filament morphology. Mol. Neurodegener. 2007, 2, 12, doi:10.1186/1750-1326-2-12.
16. Goedert, M., Cohen, E.S., Jakes, R., Cohen, P. P42 map kinase phosphorylation sites in microtubuleassociated protein tau are dephosphorylated by protein phosphatase 2a1 implications for Alzheimer’s disease. FEBS Lett. 1992, 312, 95-99.
17. Grabrucker, A.M., Rowan, M., Garner, C.C. Brain-delivery of zinc-ions as potential treatment for neurological diseases: Mini review. Drug Deliv. Lett. 2011, 1, 13-23.
18. Kwon, K.J., Lee, E.J., Cho, K.S., Cho, D.-H., Shin, C.Y., Han, S.-H. Ginkgo biloba extract (egb761) attenuates zinc-induced tau phosphorylation at ser262 by regulating gsk3β activity in rat primary cortical neurons. Food Funct. 2015, 6, 2058-2067.
19. Hirano, T., Murakami, M., Fukada, T., Nishida, K., Yamasaki, S., Suzuki, T. Roles of zinc and zinc signaling in immunity: Zinc as an intracellular signaling molecule. Adv. Immunol. 2008, 97, 149-176.
20. Deibel, M., Ehmann, W., Markesbery, W. Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: Possible relation to oxidative stress. J. Neurol. Sci. 1996, 143, 137-142.
21. Tõugu, V., Tiiman, A., Palumaa, P. Interactions of Zn(II) and Cu(II) ions with Alzheimer’s amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity. Metallomics 2011, 3, 250-261.
22. 2+-induced amyloid β-protein aggregation revealed by stopped-flow fluorescence spectroscopy. J. Phys. Chem. B 2017, 121, 3909-3917.
23. Noy, D., Solomonov, I., Sinkevich, O., Arad, T., Kjaer, K., Sagi, I. Zinc-amyloid β interactions on a millisecond time-scale stabilize non-fibrillar Alzheimer-related species. J. Am. Chem. Soc. 2008, 130, 1376-1383.
24. 3+ on amyloid-β stability, oligomerization, and aggregation amyloid-β destabilization promotes annular protofibril formation. J. Biol. Chem. 2011, 286, 9646-9656.
25. Talmard, C., Bouzan, A., Faller, P. Zinc binding to amyloid-β: Isothermal titration calorimetry and Zn competition experiments with Zn sensors. Biochemistry 2007, 46, 13658-13666.
26. Vivekanandan, S., Brender, J.R., Lee, S.Y., Ramamoorthy, A. A partially folded structure of amyloid-beta (1-40) in an aqueous environment. Biochem. Biophys. Res. Commun. 2011, 411, 312-316.
27. 2+-aβ40 complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons. J. Biol. Chem. 2012, 287, 20555-20564.
28. Tõugu, V., Karafin, A., Zovo, K., Chung, R.S., Howells, C., West, A.K., Palumaa, P. Zn(II)-and cu(II)-induced non-fibrillar aggregates of amyloid-β (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators. J. Neurochem. 2009, 110, 1784-1795.
29. Hane, F.T., Hayes, R., Lee, B.Y., Leonenko, Z. Effect of copper and zinc on the single molecule self-affinity of Alzheimer’s amyloid-β peptides. PLoS ONE 2016, 11, e0147488.
30. Sciacca, M.F., Kotler, S.A., Brender, J.R., Chen, J., Lee, D.-K., Ramamoorthy, A. Two-step mechanism of membrane disruption by aβ through membrane fragmentation and pore formation. Biophys. J. 2012, 103, 702-710.
31. Capone, R., Quiroz, F.G., Prangkio, P., Saluja, I., Sauer, A.M., Bautista, M.R., Turner, R.S., Yang, J., Mayer, M. Amyloid-β-induced ion flux in artificial lipid bilayers and neuronal cells: Resolving a controversy. Neurotox. Res. 2009, 16, 1-13.
32. Kawahara, M., Arispe, N., Kuroda, Y., Rojas, E. Alzheimer’s disease amyloid beta-protein forms Zn(2+)-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons. Biophys. J. 1997, 73, 67-75.
33. Bush, A.I., Pettingell, W., Paradis, M., Tanzi, R.E. Modulation of a beta adhesiveness and secretase site cleavage by zinc. J. Biol. Chem. 1994, 269, 12152-12158.
34. 2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-β from Alzheimer disease. J. Biol. Chem. 2010, 285, 41533-41540.
35. 2+ in humantau transfected cells. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2009, 1793, 1058-1067.
36. Esler, W.P., Stimson, E.R., Jennings, J.M., Ghilardi, J.R., Mantyh, P.W., Maggio, J.E. Zinc-induced aggregation of human and rat β-amyloid peptides in vitro. J. Neurochem. 1996, 66, 723-732.
37. Xiong, Y., Luo, D.-J., Wang, X.-L., Qiu, M., Yang, Y., Yan, X., Wang, J.-Z., Ye, Q.-F., Liu, R. Zinc binds to and directly inhibits protein phosphatase 2a in vitro. Neurosci. Bull. 2015, 31, 331-337.
38. Sun, X.-Y., Wei, Y.-P., Xiong, Y., Wang, X.-C., Xie, A.-J., Wang, X.-L., Yang, Y., Wang, Q., Lu, Y.-M., Liu, R. Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2a (pp2a). J. Biol. Chem. 2012, 287, 11174-11182.
39. Zhou, F., Chen, S., Xiong, J., Li, Y., Qu, L. Luteolin reduces zinc-induced tau phosphorylation at ser262/356 in an ros-dependent manner in sh-sy5y cells. Biol. Trace Elem. Res. 2012, 149, 273-279.
40. Squitti, R., Polimanti, R. Copper phenotype in Alzheimer’s disease: Dissecting the pathway. Am. J. Neurodegener. Dis. 2013, 2, 46-56.
41. Lech, T., Sadlik, J. Copper concentration in body tissues and fluids in normal subjects of southern Poland. Biol. Trace Elem. Res. 2007, 118, 10-15.
42. Kepp, K.P. Alzheimer’s disease due to loss of function: A new synthesis of the available data. Prog. Neurobiol. 2016, 143, 36-60.
43. White, A.R., Reyes, R., Mercer, J.F., Camakaris, J., Zheng, H., Bush, A.I., Multhaup, G., Beyreuther, K., Masters, C.L., Cappai, R. Copper levels are increased in the cerebral cortex and liver of app and aplp2 knockout mice. Brain Res. 1999, 842, 439-444.
44. Bucossi, S., Ventriglia, M., Panetta, V., Salustri, C., Pasqualetti, P., Mariani, S., Siotto, M., Rossini, P.M., Squitti, R. Copper in Alzheimer’s disease: A meta-analysis of serum, plasma, and cerebrospinal fluid studies. J. Alzheimer’s Dis. 2011, 24, 175-185.
45. Dahms, S.O., Könnig, I., Roeser, D., Gührs, K.-H., Mayer, M.C., Kaden, D., Multhaup, G., Than, M.E. Metal binding dictates conformation and function of the amyloid precursor protein (app) e2 domain. J. Mol. Biol. 2012, 416, 438-452.
46. Kitazawa, M., Cheng, D., LaFerla, F.M. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of ad. J. Neurochem. 2009, 108, 1550-1560.
47. Borchardt, T., Camakaris, J., Cappai, R., Masters, C.L., Beyreuther, K., Multhaup, G. Copper inhibits betaamyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion. Biochem. J. 1999, 344, 461-467.
48. Crouch, P.J., Hung, L.W., Adlard, P.A., Cortes, M., Lal, V., Filiz, G., Perez, K.A., Nurjono, M., Caragounis, A., Du, T. Increasing Cu bioavailability inhibits aβ oligomers and tau phosphorylation. Proc. Natl. Acad. Sci. USA 2009, 106, 381-386.
49. Voss, K., Harris, C., Ralle, M., Duffy, M., Murchison, C., Quinn, J.F. Modulation of tau phosphorylation by environmental copper. Transl. Neurodegener. 2014, 3, 24, doi:10.1186/2047-9158-3-24.
50. Soragni, A., Zambelli, B., Mukrasch, M.D., Biernat, J., Jeganathan, S., Griesinger, C., Ciurli, S., Mandelkow, E., Zweckstetter, M. Structural characterization of binding of Cu(II) to tau protein. Biochemistry 2008, 47, 10841-10851.
51. Ma, Q.F., Li, Y.M., Du, J.T., Kanazawa, K., Nemoto, T., Nakanishi, H., Zhao, Y.F. Binding of copper (II) ion to an Alzheimer’s tau peptide as revealed by MALDI-TOF MS, CD, and NMR. Biopolymers 2005, 79, 74-85.
52. Beard, J.L. Iron biology in immune function, muscle metabolism and neuronal functioning. J. Nutr. 2001, 131, 568S-580S.
53. Todorich, B., Pasquini, J.M., Garcia, C.I., Paez, P.M., Connor, J.R. Oligodendrocytes and myelination: The role of iron. Glia 2009, 57, 467-478.
54. Hare, D., Ayton, S., Bush, A., Lei, P. A delicate balance: Iron metabolism and diseases of the brain. Front. Aging Neurosci. 2013, 5, doi:10.3389/fnagi.2013.00034.
55. Schenck, J. Pathophysiology of Brain Iron, International Society for Magnetic Resonance in Medicine: Concord, CA, USA, 2010.
56. Tao, Y., Wang, Y., Rogers, J.T., Wang, F. Perturbed iron distribution in Alzheimer’s disease serum, cerebrospinal fluid, and selected brain regions: A systematic review and meta-analysis. J. Alzheimer’s Dis. 2014, 42, 679-690.
57. Mantyh, P.W., Ghilardi, J.R., Rogers, S., DeMaster, E., Allen, C.J., Stimson, E.R., Maggio, J.E. Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of β-amyloid peptide. J. Neurochem. 1993, 61, 1171-1174.
58. Liu, B., Moloney, A., Meehan, S., Morris, K., Thomas, S.E., Serpell, L.C., Hider, R., Marciniak, S.J., Lomas, D.A., Crowther, D.C. Iron promotes the toxicity of amyloid β peptide by impeding its ordered aggregation. J. Biol. Chem. 2011, 286, 4248-4256.
59. Xie, L., Zheng, W., Xin, N., Xie, J.-W., Wang, T., Wang, Z.-Y. Ebselen inhibits iron-induced tau phosphorylation by attenuating dmt1 up-regulation and cellular iron uptake. Neurochem. Int. 2012, 61, 334-340.
60. Guo, C., Wang, P., Zhong, M.-L., Wang, T., Huang, X.-S., Li, J.-Y., Wang, Z.-Y. Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem. Int. 2013, 62, 165-172.
61. Yamamoto, A., Shin, R.W., Hasegawa, K., Naiki, H., Sato, H., Yoshimasu, F., Kitamoto, T. Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: Implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J. Neurochem. 2002, 82, 1137-1147.
62. Egaña, J.T., Zambrano, C., Nuñez, M.T., Gonzalez-Billault, C., Maccioni, R.B. Iron-induced oxidative stress modify tau phosphorylation patterns in hippocampal cell cultures. Biometals 2003, 16, 215-223.
63. Ebel, H., Günther, T. Magnesium metabolism: A review. Clin. Chem. Lab. Med. 1980, 18, 257-270.
64. 2+ flux during uncorrelated activity. Neuron 2004, 44, 835-849.
65. Andrási, E., Páli, N., Molnár, Z., Kösel, S. Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J. Alzheimer’s Dis. 2005, 7, 273-284.
66. Li, W., Yu, J., Liu, Y., Huang, X., Abumaria, N., Zhu, Y., Huang, X., Xiong, W., Ren, C., Liu, X.-G. Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model. Mol. Brain 2014, 7, 65, doi:10.1186/s13041-014-0065-y.
67. Yu, J., Sun, M., Chen, Z., Lu, J., Liu, Y., Zhou, L., Xu, X., Fan, D., Chui, D. Magnesium modulates amyloid-β protein precursor trafficking and processing. J. Alzheimer’s Dis. 2010, 20, 1091-1106.
68. Ho, M., Hoke, D.E., Chua, Y.J., Li, Q.-X., Culvenor, J.G., Masters, C., White, A.R., Evin, G. Effect of metal chelators on γ-secretase indicates that calcium and magnesium ions facilitate cleavage of Alzheimer amyloid precursor substrate. Int. J. Alzheimer’s Dis. 2010, 2011, doi:10.4061/2011/950932.
69. 2+ selectively induce aggregates of phf-tau but not normal human tau. J. Neurosci. Res. 1999, 55, 36-43.
70. Xu, Z.-P., Li, L., Bao, J., Wang, Z.-H., Zeng, J., Liu, E.-J., Li, X.-G., Huang, R.-X., Gao, D., Li, M.-Z. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer’s model. PLoS ONE 2014, 9, e108645.
71. Takeda, A., Ishiwatari, S., Okada, S. Manganese uptake into rat brain during development and aging. J. Neurosci. Res. 1999, 56, 93-98.
72. Ramos, P., Santos, A., Pinto, N.R., Mendes, R., Magalhães, T., Almeida, A. Iron levels in the human brain: A post-mortem study of anatomical region differences and age-related changes. J. Trace Elem. Med. Biol. 2014, 28, 13-17.
73. Tong, Y., Yang, H., Tian, X., Wang, H., Zhou, T., Zhang, S., Yu, J., Zhang, T., Fan, D., Guo, X. High manganese, a risk for Alzheimer’s disease: High manganese induces amyloid-β related cognitive impairment. J. Alzheimer’s Dis. 2014, 42, 865-878.
74. Cai, T., Che, H., Yao, T., Chen, Y., Huang, C., Zhang, W., Du, K., Zhang, J., Cao, Y., Chen, J. Manganese induces tau hyperphosphorylation through the activation of erk mapk pathway in pc12 cells. Toxicol. Sci. 2010, 119, 169-177.
75. Liu, F., Xue, Z., Li, N., Huang, H., Ying, Y., Li, J., Wang, L., Li, W. Effects of lead exposure on the expression of amyloid β and phosphorylated tau proteins in the c57bl/6 mouse hippocampus at different life stages. J. Trace Elem. Med. Biol. 2014, 28, 227-232.
76. Basha, M.R., Wei, W., Bakheet, S.A., Benitez, N., Siddiqi, H.K., Ge, Y.-W., Lahiri, D.K., Zawia, N.H. The fetal basis of amyloidogenesis: Exposure to lead and latent overexpression of amyloid precursor protein and β-amyloid in the aging brain. J. Neurosci. 2005, 25, 823-829.
77. Bihaqi, S.W., Bahmani, A., Adem, A., Zawia, N.H. Infantile postnatal exposure to lead (pb) enhances tau expression in the cerebral cortex of aged mice: Relevance to ad. Neurotoxicology 2014, 44, 114-120.
78. Bihaqi, S.W., Zawia, N.H. Enhanced taupathy and ad-like pathology in aged primate brains decades after infantile exposure to lead (pb). Neurotoxicology 2013, 39, 95-101.
79. Dash, M., Eid, A., Subaiea, G., Chang, J., Deeb, R., Masoud, A., Renehan, W., Adem, A., Zawia, N. Developmental exposure to lead (pb) alters the expression of the human tau gene and its products in a transgenic animal model. Neurotoxicology 2016, 55, 154-159.
80. Gąssowska, M., Baranowska-Bosiacka, I., Moczydłowska, J., Tarnowski, M., Pilutin, A., Gutowska, I., Strużyńska, L., Chlubek, D., Adamczyk, A. Perinatal exposure to lead (pb) promotes tau phosphorylation in the rat brain in a gsk-3β and cdk5 dependent manner: Relevance to neurological disorders. Toxicology 2016, 347, 17-28.
81. Jiang, L.-F., Yao, T.-M., Zhu, Z.-L., Wang, C., Ji, L.-N. Impacts of Cd (II) on the conformation and selfaggregation of Alzheimer’s tau fragment corresponding to the third repeat of microtubule-binding domain. Biochim. Biophys. Acta (BBA) Proteins Proteom. 2007, 1774, 1414-1421.
82. Li, X., Lv, Y., Yu, S., Zhao, H., Yao, L. The effect of cadmium on aβ levels in app/ps1 transgenic mice. Exp. Ther. Med. 2012, 4, 125-130.
83. Del Pino, J., Zeballos, G., Anadón, M.J., Moyano, P., Díaz, M.J., García, J.M., Frejo, M.T. Cadmium-induced cell death of basal forebrain cholinergic neurons mediated by muscarinic m1 receptor blockade, increase in gsk-3β enzyme, β-amyloid and tau protein levels. Arch. Toxicol. 2016, 90, 1081-1092.
84. Ben, P., Zhang, Z., Zhu, Y., Xiong, A., Gao, Y., Mu, J., Yin, Z., Luo, L. L-theanine attenuates cadmiuminduced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Neurotoxicology 2016, 57, 95-103.
85. Hyman, M. The impact of mercury on human health and the environment. Altern. Ther. Health Med. 2004, 10, 70-75.
86. Rice, K.M., Walker, E.M., Jr., Wu, M., Gillette, C., Blough, E.R. Environmental mercury and its toxic effects. J. Prev. Med. Public Health 2014, 47, 74.
87. Olivieri, G., Brack, C., Müller-Spahn, F., Stähelin, H., Herrmann, M., Renard, P., Brockhaus, M., Hock, C. Mercury induces cell cytotoxicity and oxidative stress and increases β-amyloid secretion and tau phosphorylation in shsy5y neuroblastoma cells. J. Neurochem. 2000, 74, 231-236.
88. Chan, M.C., Bautista, E., Alvarado-Cruz, I., Quintanilla-Vega, B., Segovia, J. Inorganic mercury prevents the differentiation of sh-sy5y cells: Amyloid precursor protein, microtubule associated proteins and ros as potential targets. J. Trace Elem. Med. Biol. 2017, 41, 119-128.
89. Yang, D.J., Shi, S., Zheng, L.F., Yao, T.M., Ji, L.N. Mercury (II) promotes the in vitro aggregation of tau fragment corresponding to the second repeat of microtubule-binding domain: Coordination and conformational transition. Biopolymers 2010, 93, 1100-1107.
90. Kawahara, M., Kato, M., Kuroda, Y. Effects of aluminum on the neurotoxicity of primary cultured neurons and on the aggregation of β-amyloid protein. Brain Res. Bull. 2001, 55, 211-217.
91. Zhang, Q., Zhang, F., Ni, Y., Kokot, S. Effects of aluminum on amyloid-beta aggregation in the context of Alzheimer’s disease. Arabian J. Chem. 2015, doi:10.1016/j.arabjc.2015.06.019.
92. Walton, J. An aluminum-based rat model for Alzheimer’s disease exhibits oxidative damage, inhibition of pp2a activity, hyperphosphorylated tau, and granulovacuolar degeneration. J. Inorg. Biochem. 2007, 101, 1275-1284.
93. Prema, A., Justin Thenmozhi, A., Manivasagam, T., Mohamed Essa, M., Guillemin, G.J. Fenugreek seed powder attenuated aluminum chloride-induced tau pathology, oxidative stress, and inflammation in a rat model of Alzheimer’s disease. J. Alzheimer’s Dis. 2017, 60, S209-S220.
94. BALANCE Investigators and Collaborators, Geddes, J.R., Goodwin, G.M., Rendell, J., Azorin, J.-M., Cipriani, A., Ostacher, M.J., Morriss, R., Alder, N., Juszczak, E. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): A randomised open-label trial. Focus 2011, 9, 488-499.
95. Forlenza, O.V., De-Paula, V.d.J.R., Diniz, B. Neuroprotective effects of lithium: Implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS Chem. Neurosci. 2014, 5, 443-450.
96. Alda, M. Lithium in the treatment of bipolar disorder: Pharmacology and pharmacogenetics. Mol. Psychiatry 2015, 20, 661-670.
97. Zhang, X., Heng, X., Li, T., Li, L., Yang, D., Zhang, X., Du, Y., Doody, R.S., Le, W. Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer’s disease transgenic mouse model. J. Alzheimer’s Dis. 2011, 24, 739-749.
98. Su, Y., Ryder, J., Li, B., Wu, X., Fox, N., Solenberg, P., Brune, K., Paul, S., Zhou, Y., Liu, F. Lithium, a common drug for bipolar disorder treatment, regulates amyloid-β precursor protein processing. Biochemistry 2004, 43, 6899-6908.
99. Fu, Z.-Q., Yang, Y., Song, J., Jiang, Q., Liu, Z.-C., Wang, Q., Zhu, L.-Q., Wang, J.-Z., Tian, Q. Licl attenuates thapsigargin-induced tau hyperphosphorylation by inhibiting gsk-3β in vivo and in vitro. J. Alzheimer’s Dis. 2010, 21, 1107-1117.
100. Zhao, L., Gong, N., Liu, M., Pan, X., Sang, S., Sun, X., Yu, Z., Fang, Q., Zhao, N., Fei, G. Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer’s disease mouse model. Neurobiol. Aging 2014, 35, 2736-2745.