The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer's Disease

Zhenzhen Liu, Tao Li, Ping Li, Nannan Wei, Zhiquan Zhao, Huimin Liang, Xinying Ji, Wenwu Chen, Mengzhou Xue, Jianshe Wei, Zhenzhen Liu, Tao Li, Ping Li, Nannan Wei, Zhiquan Zhao, Huimin Liang, Xinying Ji, Wenwu Chen, Mengzhou Xue, Jianshe Wei

Abstract

Alzheimer's disease (AD) is the most common form of dementia. The pathological hallmarks of AD are amyloid plaques [aggregates of amyloid-beta (Aβ)] and neurofibrillary tangles (aggregates of tau). Growing evidence suggests that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than Aβ plaques. Oxidative stress is a prominent early event in the pathogenesis of AD and is therefore believed to contribute to tau hyperphosphorylation. Several studies have shown that the autophagic pathway in neurons is important under physiological and pathological conditions. Therefore, this pathway plays a crucial role for the degradation of endogenous soluble tau. However, the relationship between oxidative stress, tau protein hyperphosphorylation, autophagy dysregulation, and neuronal cell death in AD remains unclear. Here, we review the latest progress in AD, with a special emphasis on oxidative stress, tau hyperphosphorylation, and autophagy. We also discuss the relationship of these three factors in AD.

Figures

Figure 1
Figure 1
Tau protein NFTs formation and autophagic dysfunction in Alzheimer's disease. Aβ oligomers and ROS production intrigue oxidative stress and mitochondria dysfunction, in which induce tau protein hyperphosphorylation and neurofibrillary tangles formation with protein phosphatase and kinases imbalance. These events converge to autophagic dysfunction and tau protein aggregation to lead to neurodegeneration and cell death in AD.

References

    1. Cumming T., Brodtmann A. Dementia and stroke: the present and future epidemic. International Journal of Stroke. 2010;5(6):453–454. doi: 10.1111/j.1747-4949.2010.00527.x.
    1. Chan S. W.-C. Family caregiving in dementia: the asian perspective of a global problem. Dementia and Geriatric Cognitive Disorders. 2011;30(6):469–478. doi: 10.1159/000322086.
    1. Armstrong R. A. A critical analysis of the ‘amyloid cascade hypothesis’. Folia Neuropathologica. 2014;52(3):211–225. doi: 10.5114/fn.2014.45562.
    1. Viola K. L., Klein W. L. Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosi. Acta Neuropathologica. 2015;129(2):183–206. doi: 10.1007/s00401-015-1386-3.
    1. Paula-Lima A. C., Brito-Moreira J., Ferreira S. T. Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease. Journal of Neurochemistry. 2013;126(2):191–202. doi: 10.1111/jnc.12304.
    1. Fu A. K. Y., Hung K.-W., Huang H., et al. Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(27):9959–9964. doi: 10.1073/pnas.1405803111.
    1. De Felice F. G., Velasco P. T., Lambert M. P., et al. Aβ oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. The Journal of Biological Chemistry. 2007;282(15):11590–11601. doi: 10.1074/jbc.m607483200.
    1. Melov S., Adlard P. A., Morten K., et al. Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS ONE. 2007;2(6) doi: 10.1371/journal.pone.0000536.e536
    1. Su B., Wang X., Lee H. G., et al. Chronic oxidative stress causes increased tau phosphorylation in M17 neuroblastoma cells. Neuroscience Letters. 2010;468(3):267–271. doi: 10.1016/j.neulet.2009.11.010.
    1. Luque-Contreras D., Carvajal K., Toral-Rios D., Franco-Bocanegra D., Campos-Peña V. Oxidative stress and metabolic syndrome: cause or consequence of Alzheimer's disease? Oxidative Medicine and Cellular Longevity. 2014;2014:11. doi: 10.1155/2014/497802.497802
    1. Heras-Sandoval D., Pérez-Rojas J. M., Hernández-Damián J., Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cellular Signalling. 2014;26(12):2694–2701. doi: 10.1016/j.cellsig.2014.08.019.
    1. Saitoh Y., Fujikake N., Okamoto Y., et al. p62 plays a protective role in the autophagic degradation of polyglutamine protein oligomers in polyglutamine disease model flies. Journal of Biological Chemistry. 2015;290(3):1442–1453. doi: 10.1074/jbc.m114.590281.
    1. Ghavami S., Shojaei S., Yeganeh B., et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Progress in Neurobiology. 2014;112:24–49. doi: 10.1016/j.pneurobio.2013.10.004.
    1. Tan C.-C., Yu J.-T., Tan M.-S., Jiang T., Zhu X.-C., Tan L. Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Neurobiology of Aging. 2014;35(5):941–957. doi: 10.1016/j.neurobiolaging.2013.11.019.
    1. Salminen A., Kaarniranta K., Kauppinen A., et al. Impaired autophagy and APP processing in Alzheimer's disease: the potential role of Beclin 1 interactome. Progress in Neurobiology. 2013;106-107:33–54. doi: 10.1016/j.pneurobio.2013.06.002.
    1. Yang D.-S., Stavrides P., Saito M., et al. Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits. Brain. 2014;137(part 12):3300–3318. doi: 10.1093/brain/awu278.
    1. Nilsson P., Sekiguchi M., Akagi T., et al. Autophagy-related protein 7 deficiency in amyloid β(Aβ) precursor protein transgenic mice decreases Aβ in the multivesicular bodies and induces Aβ accumulation in the Golgi. The American Journal of Pathology. 2015;185(2):305–313. doi: 10.1016/j.ajpath.2014.10.011.
    1. Wolfe D. M., Lee J.-H., Kumar A., Lee S., Orenstein S. J., Nixon R. A. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. European Journal of Neuroscience. 2013;37(12):1949–1961. doi: 10.1111/ejn.12169.
    1. Tian Y., Chang J. C., Fan E. Y., Flajolet M., Greengard P. Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(42):17071–17076. doi: 10.1073/pnas.1315110110.
    1. Jo C., Gundemir S., Pritchard S., Jin Y. N., Rahman I., Johnson G. V. W. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nature Communications. 2014;5, article 3496 doi: 10.1038/ncomms4496.
    1. Lu T., Aron L., Zullo J., et al. REST and stress resistance in ageing and Alzheimer's disease. Nature. 2014;507(7493):448–454. doi: 10.1038/nature13163.
    1. Caccamo A., De Pinto V., Messina A., Branca C., Oddo S. Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature. Journal of Neuroscience. 2014;34(23):7988–7998. doi: 10.1523/jneurosci.0777-14.2014.
    1. Martínez E., Navarro A., Ordóñez C., del Valle E., Tolivia J. Oxidative stress induces apolipoprotein D overexpression in hippocampus during aging and alzheimer's disease. Journal of Alzheimer's Disease. 2013;36(1):129–144. doi: 10.3233/jad-130215.
    1. Zhao Y., Zhao B. Oxidative stress and the pathogenesis of alzheimer's disease. Oxidative Medicine and Cellular Longevity. 2013;2013:10. doi: 10.1155/2013/316523.316523
    1. Flynn J. M., Melovn S. SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radical Biology and Medicine. 2013;62:4–12. doi: 10.1016/j.freeradbiomed.2013.05.027.
    1. Holley A. K., Bakthavatchalu V., Velez-Roman J. M., St. Clair D. K. Manganese superoxide dismutase: guardian of the powerhouse. International Journal of Molecular Sciences. 2011;12(10):7114–7162. doi: 10.3390/ijms12107114.
    1. Mattson M. P., Magnus T. Ageing and neuronal vulnerability. Nature Reviews Neuroscience. 2006;7(4):278–294. doi: 10.1038/nrn1886.
    1. Chen L., Na R., Ran Q. Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline. Neurobiology of Aging. 2014;35(11):2552–2561. doi: 10.1016/j.neurobiolaging.2014.05.007.
    1. Yamazaki D., Horiuchi J., Ueno K., et al. Glial dysfunction causes age-related memory impairment in Drosophila . Neuron. 2014;84(4):753–763. doi: 10.1016/j.neuron.2014.09.039.
    1. Tayler H., Fraser T., Miners J. S., Kehoe P. G., Love S. Oxidative balance in Alzheimer's disease: relationship to APOE, braak tangle stage, and the concentrations of soluble and insoluble amyloid-β . Journal of Alzheimer's Disease. 2010;22(4):1363–1373. doi: 10.3233/jad-2010-101368.
    1. Han B. H., Zhou M. L., Johnson A. W., et al. Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice. Proceedings of The National Academy of Sciences of The United States of America. 2015;112(8):E881–E890. doi: 10.1073/pnas.1414930112.
    1. Nordström P., Michaëlsson K., Gustafson Y., Nordström A. Traumatic brain injury and young onset dementia: a nationwide cohort study. Annals of Neurology. 2014;75(3):374–381. doi: 10.1002/ana.24101.
    1. Zhou J., Yu J. T., Wang H. F., et al. Association between stroke and Alzheimer's disease: systematic review and meta-analysis. Journal of Alzheimers Disease. 2015;43(2):479–489.
    1. Cifuentes D., Poittevin M., Dere E., et al. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease. Hypertension. 2015;65(1):218–224. doi: 10.1161/hypertensionaha.114.04139.
    1. Barbagallo M., Dominguez L. J. Type 2 diabetes mellitus and Alzheimer's disease. The World Journal of Diabetes. 2014;5(6):889–893. doi: 10.4239/wjd.v5.i6.889.
    1. Park S. H., Kim J. H., Choi K. H., et al. Hypercholesterolemia accelerates amyloid β-induced cognitive deficits. International Journal of Molecular Medicine. 2013;31(3):577–582. doi: 10.3892/ijmm.2013.1233.
    1. Nazef K., Khelil M., Chelouti H., et al. Hyperhomocysteinemia is a risk factor for Alzheimer's disease in an Algerian population. Archives of Medical Research. 2014;45(3):247–250. doi: 10.1016/j.arcmed.2014.03.001.
    1. VanDuyn N., Settivari R., LeVora J., Zhou S., Unrine J., Nass R. The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration. Journal of Neurochemistry. 2013;124(1):147–157. doi: 10.1111/jnc.12072.
    1. Durazzo T. C., Mattsson N., Weiner M. W. Smoking and increased Alzheimer's disease risk: a review of potential mechanisms. Alzheimers and Dementia. 2014;10(3):S122–S145. doi: 10.1016/j.jalz.2014.04.009.
    1. Pasinetti G. M., Eberstein J. A. Metabolic syndrome and the role of dietary lifestyles in Alzheimer's disease. Journal of Neurochemistry. 2008;106(4):1503–1514. doi: 10.1111/j.1471-4159.2008.05454.x.
    1. Littlejohns T. J., Henley W. E., Lang I. A., et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83(10):920–928. doi: 10.1212/wnl.0000000000000755.
    1. Ohia-Nwoko O., Montazari S., Lau Y.-S., Eriksen J. L. Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice. Molecular Neurodegeneration. 2014;9, article 54 doi: 10.1186/1750-1326-9-54.
    1. Nunomura A., Castellani R. J., Zhu X., Moreira P. I., Perry G., Smith M. A. Involvement of oxidative stress in Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2006;65(7):631–641. doi: 10.1097/.
    1. Vemuri P., Lesnick T. G., Przybelski S. A., et al. Effect of lifestyle activities on alzheimer disease biomarkers and cognition. Annals of Neurology. 2012;72(5):730–738. doi: 10.1002/ana.23665.
    1. Antoniou M., Gunasekera G. M., Wong P. C. M. Foreign language training as cognitive therapy for age-related cognitive decline: a hypothesis for future research. Neuroscience and Biobehavioral Reviews. 2013;37, part 2:2689–2698. doi: 10.1016/j.neubiorev.2013.09.004.
    1. Yao J., Irwin R. W., Zhao L., Nilsen J., Hamilton R. T., Brinton R. D. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(34):14670–14675. doi: 10.1073/pnas.0903563106.
    1. García-Escudero V., Martín-Maestro P., Perry G., Avila J. Deconstructing mitochondrial dysfunction in alzheimer disease. Oxidative Medicine and Cellular Longevity. 2013;2013:13. doi: 10.1155/2013/162152.162152
    1. Mondragón-Rodríguez S., Perry G., Zhu X., Moreira P. I., Acevedo-Aquino M. C., Williams S. Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer's disease. Oxidative Medicine and Cellular Longevity. 2013;2013:6. doi: 10.1155/2013/940603.940603
    1. Yao J., Du H., Yan S., et al. Inhibition of amyloid-beta (Abeta) peptide-binding alcohol dehydrogenase-Abeta interaction reduces Abeta accumulation and improves mitochondrial function in a mouse model of Alzheimer's disease. Journal of Neuroscience. 2011;31(6):2313–2320. doi: 10.1523/JNEUROSCI.4717-10.2011.
    1. Pensalfini A., Zampagni M., Liguri G., et al. Membrane cholesterol enrichment prevents Aβ-induced oxidative stress in Alzheimer's fibroblasts. Neurobiology of Aging. 2011;32(2):210–222. doi: 10.1016/j.neurobiolaging.2009.02.010.
    1. Schuessel K., Schäfer S., Bayer T. A., et al. Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiology of Disease. 2005;18(1):89–99. doi: 10.1016/j.nbd.2004.09.003.
    1. Dumont M., Stack C., Elipenahli C., et al. Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. The FASEB Journal. 2011;25(11):4063–4072. doi: 10.1096/fj.11-186650.
    1. Murakami K., Murata N., Noda Y., et al. SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid β protein oligomerization and memory loss in mouse model of Alzheimer disease. The Journal of Biological Chemistry. 2011;286(52):44557–44568. doi: 10.1074/jbc.m111.279208.
    1. Poppek D., Keck S., Ermak G., et al. Phosphorylation inhibits turnover of the tau protein by the proteasome: influence of RCAN1 and oxidative stress. Biochemical Journal. 2006;400(3):511–520. doi: 10.1042/bj20060463.
    1. Melov S., Adlard P. A., Morten K., et al. Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS ONE. 2007;2(6, article e536) doi: 10.1371/journal.pone.0000536.
    1. Morita T., Sobuě K. Specification of neuronal polarity regulated by local translation of CRMP2 and tau via the mTOR-p70S6K pathway. Journal of Biological Chemistry. 2009;284(40):27734–27745. doi: 10.1074/jbc.M109.008177.
    1. Li L., Fothergill T., Hutchins B. I., Dent E. W., Kalil K. Wnt5a evokes cortical axon outgrowth and repulsive guidance by tau mediated reorganization of dynamic microtubules. Developmental Neurobiology. 2014;74(8):797–817. doi: 10.1002/dneu.22102.
    1. Fuster-Matanzo A., Llorens-Martín M., Jurado-Arjona J., Avila J., Hernández F. Tau protein and adult hippocampal neurogenesis. Frontiers in Neuroscience. 2012;6, article 104 doi: 10.3389/fnins.2012.00104.
    1. Avila J., Lucas J. J., Pérez M., Hernández F. Role of Tau protein in both physiological and pathological conditions. Physiological Reviews. 2004;84(2):361–384. doi: 10.1152/physrev.00024.2003.
    1. Gordon D., Kidd G. J., Smith R. Antisense suppression of tau in cultured rat oligodendrocytes inhibits process formation. Journal of Neuroscience Research. 2008;86(12):2591–2601. doi: 10.1002/jnr.21719.
    1. Kolarova M., García-Sierra F., Bartos A., Ricny J., Ripova D. Structure and pathology of tau protein in Alzheimer disease. International Journal of Alzheimer's Disease. 2012;2012:13. doi: 10.1155/2012/731526.731526
    1. Fauquant C., Redeker V., Landrieu I., et al. Systematic identification of tubulin-interacting fragments of the microtubule-associated protein Tau leads to a highly efficient promoter of microtubule assembly. Journal of Biological Chemistry. 2011;286(38):33358–33368. doi: 10.1074/jbc.M111.223545.
    1. Li H.-L., Wang H.-H., Liu S.-J., et al. Phosphorylation of tau antagonizes apoptosis by stabilizing beta-catenin, a mechanism involved in Alzheimer's neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(9):3591–3596. doi: 10.1073/pnas.0609303104.
    1. Rodríguez-Martín T., Cuchillo-Ibáñez I., Noble W., Nyenya F., Anderton B. H., Hanger D. P. Tau phosphorylation affects its axonal transport and degradation. Neurobiology of Aging. 2013;34(9):2146–2157. doi: 10.1016/j.neurobiolaging.2013.03.015.
    1. Ballatore C., Brunden K. R., Huryn D. M., Trojanowski J. Q., Lee V. M.-Y., Smith A. B. Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies. Journal of Medicinal Chemistry. 2012;55(21):8979–8996. doi: 10.1021/jm301079z.
    1. Simón D., García-García E., Royo F., Falcón-Pérez J. M., Avila J. Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Letters. 2012;586(1):47–54. doi: 10.1016/j.febslet.2011.11.022.
    1. Qian W., Liu F. Regulation of alternative splicing of tau exon 10. Neuroscience Bulletin. 2014;30(2):367–377. doi: 10.1007/s12264-013-1411-2.
    1. Liu F., Gong C.-X. Tau exon 10 alternative splicing and tauopathies. Molecular Neurodegeneration. 2008;3(1, article 8) doi: 10.1186/1750-1326-3-8.
    1. Jovanov-Milošević N., Petrović D., Sedmak G., Vukšić M., Hof P. R., Šimić G. Human fetal tau protein isoform: possibilities for Alzheimer's disease treatment. The International Journal of Biochemistry & Cell Biology. 2012;44(8):1290–1294. doi: 10.1016/j.biocel.2012.05.001.
    1. Adams S. J., de Ture M. A., McBride M., Dickson D. W., Petrucelli L. Three repeat isoforms of tau inhibit assembly of four repeat tau filaments. PLoS ONE. 2010;5(5) doi: 10.1371/journal.pone.0010810.e10810
    1. Espinoza M., de Silva R., Dickson D. W., Davies P. Differential incorporation of tau isoforms in Alzheimer's disease. Journal of Alzheimer's Disease. 2008;14(1):1–16.
    1. Fernández-Nogales M., Cabrera J. R., Santos-Galindo M., et al. Huntington's disease is a four-repeat tauopathy with tau nuclear rods. Nature Medicine. 2014;20(8):881–885. doi: 10.1038/nm.3617.
    1. Glatz D. C., Rujescu D., Tang Y., et al. The alternative splicing of tau exon 10 and its regulatory proteins CLK2 and TRA2-BETA1 changes in sporadic Alzheimer's disease. Journal of Neurochemistry. 2006;96(3):635–644. doi: 10.1111/j.1471-4159.2005.03552.x.
    1. Niblock M. J., Gallo J. M. Tau alternative splicing in familial and sporadic tauopathies. Biochemical Society Transactions. 2012;40(4):677–680. doi: 10.1042/bst20120091.
    1. Yoshiyama Y., Lee V. M. Y., Trojanowski J. Q. Therapeutic strategies for tau mediated neurodegeneration. Journal of Neurology, Neurosurgery & Psychiatry. 2013;84(7):784–795. doi: 10.1136/jnnp-2012-303144.
    1. Iijima-Ando K., Zhao L., Gatt A., Shenton C., Iijima K. A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration. Human Molecular Genetics. 2010;19(10):1930–1938. doi: 10.1093/hmg/ddq068.
    1. Mendoza J., Sekiya M., Taniguchi T., Iijima K. M., Wang R., Ando K. Global analysis of phosphorylation of Tau by the checkpoint kinases Chk1 and Chk2 in vitro. Journal of Proteome Research. 2013;12(6):2654–2665. doi: 10.1021/pr400008f.
    1. Flunkert S., Hierzer M., Löffler T., et al. Elevated levels of soluble total and hyperphosphorylated tau result in early behavioral deficits and distinct changes in brain pathology in a new tau transgenic mouse model. American Journal of Neurodegenerative Disease. 2013;11(4):194–205. doi: 10.1159/000338152.
    1. Gong C.-X., Iqbal K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Current Medicinal Chemistry. 2008;15(23):2321–2328. doi: 10.2174/092986708785909111.
    1. Kiris E., Ventimiglia D., Sargin M. E., et al. Combinatorial Tau pseudophosphorylation: markedly different regulatory effects on microtubule assembly and dynamic instability than the sum of the individual parts. The Journal of Biological Chemistry. 2011;286(16):14257–14270. doi: 10.1074/jbc.m111.219311.
    1. Hernandez F., Lucas J. J., Avila J. GSK3 and tau: two convergence points in Alzheimer's disease. Journal of Alzheimer's Disease. 2013;33(1):S141–S144. doi: 10.3233/jad-2012-129025.
    1. Gao C., Hölscher C., Liu Y., Li L. GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease. Reviews in the Neurosciences. 2011;23(1):1–11. doi: 10.1515/rns.2011.061.
    1. Gandy J. C., Melendez-Ferro M., Bijur G. N., et al. Glycogen synthase kinase-3β (GSK3β) expression in a mouse model of Alzheimer's disease: a light and electron microscopy study. Synapse. 2013;67(6):313–327. doi: 10.1002/syn.21642.
    1. Maldonado H., Ramírez E., Utreras E., et al. Inhibition of cyclin-dependent kinase 5 but not of glycogen synthase kinase 3-β prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T-cell leukemia virus type I-infected lymphocytes. Journal of Neuroscience Research. 2011;89(9):1489–1498. doi: 10.1002/jnr.22678.
    1. López-Tobón A., Castro-Álvarez J. F., Piedrahita D., Boudreau R. L., Gallego-Gómez J. C., Cardona-Gómez G. P. Silencing of CDK5 as potential therapy for Alzheimer's disease. Reviews in the Neurosciences. 2011;22(2):143–152. doi: 10.1515/RNS.2011.015.
    1. Corrêa S. A. L., Eales K. L. The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease. Journal of Signal Transduction. 2012;2012:12. doi: 10.1155/2012/649079.649079
    1. Li G., Yin H., Kuret J. Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. Journal of Biological Chemistry. 2004;279(16):15938–15945. doi: 10.1074/jbc.m314116200.
    1. Liu F., Liang Z., Shi J., et al. PKA modulates GSK-3β- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners. FEBS Letters. 2006;580(26):6269–6274. doi: 10.1016/j.febslet.2006.10.033.
    1. Tsukane M., Yamauchi T. Ca2+/calmodulin-dependent protein kinase II mediates apoptosis of P19 cells expressing human tau during neural differentiation with retinoic acid treatment. Journal of Enzyme Inhibition and Medicinal Chemistry. 2009;24(2):365–371.
    1. Liu F., Grundke-Iqbal I., Iqbal K., Gong C.-X. Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. European Journal of Neuroscience. 2005;22(8):1942–1950. doi: 10.1111/j.1460-9568.2005.04391.x.
    1. Landrieu I., Smet-Nocca C., Amniai L., et al. Molecular implication of PP2A and Pin1 in the Alzheimer's disease specific hyperphosphorylation of Tau. PLoS ONE. 2011;6(6) doi: 10.1371/journal.pone.0021521.e21521
    1. Rudrabhatla P., Pant H. C. Role of protein phosphatase 2A in Alzheimer's disease. Current Alzheimer Research. 2011;8(6):623–632. doi: 10.2174/156720511796717168.
    1. Park S. S., Jung H.-J., Kim Y.-J., et al. Asp664 cleavage of amyloid precursor protein induces tau phosphorylation by decreasing protein phosphatase 2A activity. Journal of Neurochemistry. 2012;123(5):856–865. doi: 10.1111/jnc.12032.
    1. Liang Z., Liu F., Iqbal K., Grundke-Iqbal I., Wegiel J., Gong C. X. Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome. Journal of Alzheimer's Disease. 2008;13(3):295–302.
    1. Martin L., Latypova X., Wilson C. M., Magnaudeix A., Perrin M.-L., Terro F. Tau protein phosphatases in Alzheimer's disease: the leading role of PP2A. Ageing Research Reviews. 2013;12(1):39–49. doi: 10.1016/j.arr.2012.06.008.
    1. Arif M., Wei J., Zhang Q., et al. Cytoplasmic retention of protein phosphatase 2A-inhibitor 2 (I2PP2A) induces Alzheimer-like abnormal hyperphosphorylation of Tau. The Journal of Biological Chemistry. 2014;289(40):27677–27691. doi: 10.1074/jbc.m114.565358.
    1. Arnaud L., Chen S., Liu F., et al. Mechanism of inhibition of PP2A activity and abnormal hyperphosphorylation of tau by I2(PP2A)/SET. FEBS Letters. 2011;585(17):2653–2659. doi: 10.1016/j.febslet.2011.07.020.
    1. Liu G.-P., Zhang Y., Yao X.-Q., et al. Activation of glycogen synthase kinase-3 inhibits protein phosphatase-2A and the underlying mechanisms. Neurobiology of Aging. 2008;29(9):1348–1358. doi: 10.1016/j.neurobiolaging.2007.03.012.
    1. Kamat P. K., Rai S., Nath C. Okadaic acid induced neurotoxicity: an emerging tool to study Alzheimer's disease pathology. NeuroToxicology. 2013;37:163–172. doi: 10.1016/j.neuro.2013.05.002.
    1. Patil S., Chan C. Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. Neuroscience Letters. 2005;384(3):288–293. doi: 10.1016/j.neulet.2005.05.003.
    1. Lovell M. A., Xiong S., Xie C., Davies P., Markesbery W. R. Induction of hyperphosphorylated tau in primary rat cortical neuron cultures mediated by oxidative stress and glycogen synthase kinase-3. Journal of Alzheimer's Disease. 2004;6(6):659–671.
    1. Zambrano C. A., Egaña J. T., Núñez M. T., Maccioni R. B., González-Billault C. Oxidative stress promotes τ dephosphorylation in neuronal cells: the roles of cdk5 and PP1. Free Radical Biology and Medicine. 2004;36(11):1393–1402. doi: 10.1016/j.freeradbiomed.2004.03.007.
    1. Dias-Santagata D., Fulga T. A., Duttaroy A., Feany M. B. Oxidative stress mediates tau-induced neurodegeneration in Drosophila . The Journal of Clinical Investigation. 2007;117(1):236–245. doi: 10.1172/jci28769.
    1. Frost B., Hemberg M., Lewis J., Feany M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nature Neuroscience. 2014;17(3):357–366. doi: 10.1038/nn.3639.
    1. Khurana V. Modeling tauopathy in the fruit fly Drosophila melanogaster . Journal of Alzheimer's Disease. 2008;15(4):541–553.
    1. Su X.-Y., Wu W.-H., Huang Z.-P., et al. Hydrogen peroxide can be generated by tau in the presence of Cu(II) Biochemical and Biophysical Research Communications. 2007;358(2):661–665. doi: 10.1016/j.bbrc.2007.04.191.
    1. Feng Y., Xia Y., Yu G., et al. Cleavage of GSK-3β by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK-3β activity induced by H2O2 . Journal of Neurochemistry. 2013;126(2):234–242. doi: 10.1111/jnc.12285.
    1. Chiara F., Gambalunga A., Sciacovelli M., et al. Chemotherapeutic induction of mitochondrial oxidative stress activates GSK-3α/β and Bax, leading to permeability transition pore opening and tumor cell death. Cell Death and Disease. 2012;3(12, article e444) doi: 10.1038/cddis.2012.184.
    1. Cho M.-H., Kim D.-H., Choi J.-E., Chang E.-J. Increased phosphorylation of dynamin-related protein 1 and mitochondrial fission in okadaic acid-treated neurons. Brain Research. 2012;1454:100–110. doi: 10.1016/j.brainres.2012.03.010.
    1. Chen L., Liu L., Huang S. Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Radical Biology and Medicine. 2008;45(7):1035–1044. doi: 10.1016/j.freeradbiomed.2008.07.011.
    1. Beydoun M. A., Fanelli-Kuczmarski M. T., Kitner-Triolo M. H., et al. Dietary antioxidant intake and its association with cognitive function in an ethnically diverse sample of US adults. Psychosomatic Medicine. 2015;77(1):68–82. doi: 10.1097/psy.0000000000000129.
    1. Gillette-Guyonnet S., Secher M., Vellas B. Nutrition and neurodegeneration: epidemiological evidence and challenges for future research. British Journal of Clinical Pharmacology. 2013;75(3):738–755.
    1. Beydoun M. A., Beydoun H. A., Gamaldo A. A., Teel A., Zonderman A. B., Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014;14, article 643 doi: 10.1186/1471-2458-14-643.
    1. Hamaguchi T., Ono K., Murase A., Yamada M. Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloid-beta aggregation pathway. The American Journal of Pathology. 2009;175(6):2557–2565. doi: 10.2353/ajpath.2009.090417.
    1. Teixeira J., Silva T., Andrade P. B., Borges F. Alzheimer's disease and antioxidant therapy: how long how far? Current Medicinal Chemistry. 2013;20(24):2939–2952. doi: 10.2174/1871523011320240001.
    1. Peng C.-X., Hu J., Liu D., et al. Disease-modified glycogen synthase kinase-3β intervention by melatonin arrests the pathology and memory deficits in an Alzheimer's animal model. Neurobiology of Aging. 2013;34(6):1555–1563. doi: 10.1016/j.neurobiolaging.2012.12.010.
    1. Benítez-King G., Ortíz-López L., Jiménez-Rubio G., Ramírez-Rodríguez G. Haloperidol causes cytoskeletal collapse in N1E-115 cells through tau hyperphosphorylation induced by oxidative stress: implications for neurodevelopment. European Journal of Pharmacology. 2010;644(1–3):24–31. doi: 10.1016/j.ejphar.2010.06.057.
    1. Li X.-C., Wang Z.-F., Zhang J.-X., Wang Q., Wang J.-Z. Effect of melatonin on calyculin A-induced tau hyperphosphorylation. European Journal of Pharmacology. 2005;510(1-2):25–30. doi: 10.1016/j.ejphar.2005.01.023.
    1. Hoppe J. B., Frozza R. L., Horn A. P., et al. Amyloid-β neurotoxicity in organotypic culture is attenuated by melatonin: involvement of GSK-3β, tau and neuroinflammation. Journal of Pineal Research. 2010;48(3):230–238. doi: 10.1111/j.1600-079x.2010.00747.x.
    1. Lin L., Huang Q.-X., Yang S.-S., Chu J., Wang J.-Z., Tian Q. Melatonin in Alzheimer's disease. International Journal of Molecular Sciences. 2013;14(7):14575–14593. doi: 10.3390/ijms140714575.
    1. Galasko D. R., Peskind E., Clark C. M., et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Archives of Neurology. 2012;69(7):836–841. doi: 10.1001/archneurol.2012.85.
    1. Cente M., Filipcik P., Mandakova S., Zilka N., Krajciova G., Novak M. Expression of a truncated human tau protein induces aqueous-phase free radicals in a rat model of tauopathy: implications for targeted antioxidative therapy. Journal of Alzheimer's Disease. 2009;17(4):913–920. doi: 10.3233/jad-2009-1107.
    1. Yoon I., Kwang H. L., Cho J. Gossypin protects primary cultured rat cortical cells from oxidative stress- and β-amyloid-induced toxicity. Archives of Pharmacal Research. 2004;27(4):454–459. doi: 10.1007/BF02980089.
    1. Rajasekar N., Dwivedi S., Tota S. K., et al. Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice. European Journal of Pharmacology. 2013;715(1–3):381–394. doi: 10.1016/j.ejphar.2013.04.033.
    1. Villaflores O. B., Chen Y.-J., Chen C.-P., Yeh J.-M., Wu T.-Y. Effects of curcumin and demethoxycurcumin on amyloid-β precursor and tau proteins through the internal ribosome entry sites: a potential therapeutic for Alzheimer's disease. Taiwanese Journal of Obstetrics & Gynecology. 2012;51(4):554–564. doi: 10.1016/j.tjog.2012.09.010.
    1. Ma Q.-L., Zuo X., Yang F., et al. Curcumin suppresses soluble tau dinners and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. Journal of Biological Chemistry. 2013;288(6):4056–4065. doi: 10.1074/jbc.m112.393751.
    1. Mutsuga M., Chambers J. K., Uchida K., et al. Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer's brain. The Journal of Veterinary Medical Science. 2012;74(1):51–57. doi: 10.1292/jvms.11-0307.
    1. Stuerenburg H. J., Ganzer S., Müller-Thomsen T. Plasma betacarotene in Alzheimer's disease—association with cerebrospinal fluid beta-amyloid 1-40, (Abeta40), beta-amyloid 1-42 (Abeta42) and total Tau. Neuroendocrinology Letters. 2005;26(6):696–698.
    1. Chen Y., Wang C., Hu M., et al. Effects of ginkgolide a on okadaic acid-induced tau hyperphosphorylation and the PI3K-Akt signaling pathway in N2a cells. Planta Medica. 2012;78(12):1337–1341. doi: 10.1055/s-0032-1314965.
    1. Defeudis F. V. Bilobalide and neuroprotection. Pharmacological Research. 2002;46(6):565–568. doi: 10.1016/s1043-6618(02)00233-5.
    1. Frake R. A., Ricketts T., Menzies F. M., Rubinsztein D. C. Autophagy and neurodegeneration. The Journal of Clinical Investigation. 2015;125(1):65–74.
    1. Damme M., Suntio T., Saftig P., Eskelinen E.-L. Autophagy in neuronal cells: general principles and physiological and pathological functions. Acta Neuropathologica. 2015;129(3):337–362. doi: 10.1007/s00401-014-1361-4.
    1. Yamamoto A., Yue Z. Autophagy and its normal and pathogenic states in the brain. Annual Review of Neuroscience. 2014;37(1):55–78. doi: 10.1146/annurev-neuro-071013-014149.
    1. Nixon R. A. The role of autophagy in neurodegenerative disease. Nature Medicine. 2013;19(8):983–997. doi: 10.1038/nm.3232.
    1. Efeyan A., Comb W. C., Sabatini D. M. Nutrient-sensing mechanisms and pathways. Nature. 2015;517(7534):302–310. doi: 10.1038/nature14190.
    1. Bové J., Martínez-Vicente M., Vila M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nature Reviews Neuroscience. 2011;12(8):437–452. doi: 10.1038/nrn3068.
    1. Funderburk S. F., Marcellino B. K., Yue Z. Cell ‘self-eating’ (autophagy) mechanism in Alzheimer's disease. Mount Sinai Journal of Medicine. 2010;77(1):59–68. doi: 10.1002/msj.20161.
    1. Li L., Zhang X., Le W. Autophagy dysfunction in Alzheimer's disease. American Journal of Neurodegenerative Disease. 2010;7(4):265–271. doi: 10.1159/000276710.
    1. Ułamek-Kozioł M., Furmaga-Jabłońska W., Januszewski S., et al. Neuronal autophagy: self-eating or self-cannibalism in Alzheimer's disease. Neurochemical Research. 2013;38(9):1769–1773. doi: 10.1007/s11064-013-1082-4.
    1. Jewell J. L., Russell R. C., Guan K. L. Amino acid signalling upstream of mTOR. Nature Reviews Molecular Cell Biology. 2013;14(3):133–139. doi: 10.1038/nrm3522.
    1. Cai Z., Yan L. J. Rapamycin, autophagy, and Alzheimer's disease. Journal of Biochemical and Pharmacological Research. 2013;1(2):84–90.
    1. Dunlop E. A., Tee A. R. The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis. Biochemical Society Transactions. 2013;41(4):939–943. doi: 10.1042/bst20130030.
    1. Ishizuka Y., Kakiya N., Witters L. A., et al. AMP-activated protein kinase counteracts brain-derived neurotrophic factor-induced mammalian target of rapamycin complex 1 signaling in neurons. Journal of Neurochemistry. 2013;127(1):66–77. doi: 10.1111/jnc.12362.
    1. Jung C. H., Seo M., Otto N. M., Kim D.-H. ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011;7(10):1212–1221. doi: 10.4161/auto.7.10.16660.
    1. Maiuri M. C., Malik S. A., Morselli E., et al. Stimulation of autophagy by the p53 target gene Sestrin2. Cell Cycle. 2009;8(10):1571–1576. doi: 10.4161/cc.8.10.8498.
    1. Chan E. Y. W., Longatti A., McKnight N. C., Tooze S. A. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Molecular and Cellular Biology. 2009;29(1):157–171. doi: 10.1128/mcb.01082-08.
    1. Sarkar S., Floto R. A., Berger Z., et al. Lithium induces autophagy by inhibiting inositol monophosphatase. Journal of Cell Biology. 2005;170(7):1101–1111. doi: 10.1083/jcb.200504035.
    1. Zou J., Yue F., Jiang X., Li W., Yi J., Liu L. Mitochondrion-associated protein LRPPRC suppresses the initiation of basal levels of autophagy via enhancing Bcl-2 stability. Biochemical Journal. 2013;454(3):447–457. doi: 10.1042/BJ20130306.
    1. Alirezaei M., Kiosses W. B., Fox H. S. Decreased neuronal autophagy in HIV dementia: a mechanism of indirect neurotoxicity. Autophagy. 2008;4(7):963–966. doi: 10.4161/auto.6805.
    1. Shpilka T., Weidberg H., Pietrokovski S., Elazar Z. Atg8: an autophagy-related ubiquitin-like protein family. Genome Biology. 2011;12(7, article 226) doi: 10.1186/gb-2011-12-7-226.
    1. Kang R., Zeh H. J., Lotze M. T., Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death and Differentiation. 2011;18(4):571–580. doi: 10.1038/cdd.2010.191.
    1. Lünemann J. D., Schmidt J., Schmid D., et al. β-Amyloid is a substrate of autophagy in sporadic inclusion body myositis. Annals of Neurology. 2007;61(5):476–483. doi: 10.1002/ana.21115.
    1. Jaeger P. A., Pickford F., Sun C.-H., Lucin K. M., Masliah E., Wyss-Coray T. Regulation of amyloid precursor protein processing by the beclin 1 complex. PLoS ONE. 2010;5(6) doi: 10.1371/journal.pone.0011102.e11102
    1. Ma J. F., Huang Y., Chen S. D., Halliday G. Immunohistochemical evidence for macroautophagy in neurones and endothelial cells in Alzheimer's disease. Neuropathology and Applied Neurobiology. 2010;36(4):312–319. doi: 10.1111/j.1365-2990.2010.01067.x.
    1. Yu W. H., Cuervo A. M., Kumar A., et al. Macroautophagy—a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease. The Journal of Cell Biology. 2005;171(1):87–98. doi: 10.1083/jcb.200505082.
    1. Perucho J., Casarejos M. J., Gomez A., Solano R. M., de Yébenes J. G., Mena M. A. Trehalose protects from aggravation of amyloid pathology induced by isoflurane anesthesia in APPswe mutant mice. Current Alzheimer Research. 2012;9(3):334–343. doi: 10.2174/156720512800107573.
    1. Lai A. Y., McLaurin J. Inhibition of amyloid-beta peptide aggregation rescues the autophagic deficits in the TgCRND8 mouse model of Alzheimer disease. Biochimica et Biophysica Acta—Molecular Basis of Disease. 2012;1822(10):1629–1637. doi: 10.1016/j.bbadis.2012.07.003.
    1. Wei J., Fujita M., Nakai M., et al. Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies. The American Journal of Pathology. 2009;174(5):1891–1909. doi: 10.2353/ajpath.2009.080680.
    1. Nixon R. A., Yang D.-S., Lee J.-H. Neurodegenerative lysosomal disorders: a continuum from development to late age. Autophagy. 2008;4(5):590–599. doi: 10.4161/auto.6259.
    1. Cardoso S. M., Pereira C. F., Moreira P. I., Arduino D. M., Esteves A. R., Oliveira C. R. Mitochondrial control of autophagic lysosomal pathway in Alzheimer's disease. Experimental Neurology. 2010;223(2):294–298. doi: 10.1016/j.expneurol.2009.06.008.
    1. Silva D. F. F., Esteves A. R., Arduino D. M., Oliveira C. R., Cardoso S. M. Amyloid-β-induced mitochondrial dysfunction impairs the autophagic lysosomal pathway in a tubulin dependent pathway. Journal of Alzheimer's Disease. 2011;26(3):565–581. doi: 10.3233/jad-2011-110423.
    1. Wang Y., Mandelkow E. Degradation of tau protein by autophagy and proteasomal pathways. Biochemical Society Transactions. 2012;40(4):644–652. doi: 10.1042/BST20120071.
    1. Caccamo A., Magrì A., Medina D. X., et al. mTOR regulates tau phosphorylation and degradation: implications for Alzheimer's disease and other tauopathies. Aging Cell. 2013;12(3):370–380. doi: 10.1111/acel.12057.
    1. Liu Y., Su Y., Wang J., et al. Rapamycin decreases tau phosphorylation at Ser214 through regulation of cAMP-dependent kinase. Neurochemistry International. 2013;62(4):458–467. doi: 10.1016/j.neuint.2013.01.014.
    1. Ozcelik S., Fraser G., Castets P., et al. Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. PLoS ONE. 2013;8(5) doi: 10.1371/journal.pone.0062459.e62459
    1. Dolan P. J., Johnson G. V. W. A caspase cleaved form of tau is preferentially degraded through the autophagy pathway. The Journal of Biological Chemistry. 2010;285(29):21978–21987. doi: 10.1074/jbc.m110.110940.
    1. Krüger U., Wang Y., Kumar S., Mandelkow E.-M. Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiology of Aging. 2012;33(10):2291–2305. doi: 10.1016/j.neurobiolaging.2011.11.009.
    1. Kim S.-I., Lee W.-K., Kang S.-S., et al. Suppression of autophagy and activation of glycogen synthase kinase 3beta facilitate the aggregate formation of tau. The Korean Journal of Physiology & Pharmacology. 2011;15(2):107–114. doi: 10.4196/kjpp.2011.15.2.107.
    1. Lim F., Hernández F., Lucas J. J., Gómez-Ramos P., Morán M. A., Ávila J. FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and tau filaments in forebrain. Molecular and Cellular Neuroscience. 2001;18(6):702–714. doi: 10.1006/mcne.2001.1051.
    1. Lin W.-L., Lewis J., Yen S.-H., Hutton M., Dickson D. W. Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tau. Journal of Neurocytology. 2003;32(9):1091–1105. doi: 10.1023/B:NEUR.0000021904.61387.95.
    1. Magnaudeix A., Wilson C. M., Page G., et al. PP2A blockade inhibits autophagy and causes intraneuronal accumulation of ubiquitinated proteins. Neurobiology of Aging. 2013;34(3):770–790. doi: 10.1016/j.neurobiolaging.2012.06.026.
    1. Yoon S. Y., Choi J. E., Kweon H.-S., et al. Okadaic acid increases autophagosomes in rat neurons: implications for Alzheimer's disease. Journal of Neuroscience Research. 2008;86(14):3230–3239. doi: 10.1002/jnr.21760.
    1. Hamano T., Gendron T. F., Causevic E., et al. Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression. European Journal of Neuroscience. 2008;27(5):1119–1130. doi: 10.1111/j.1460-9568.2008.06084.x.
    1. Wang Y., Martinez-Vicente M., Krüger U., et al. Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Human Molecular Genetics. 2009;18(21):4153–4170. doi: 10.1093/hmg/ddp367.

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