Keywords: Alpha Secretase, Amyloid Beta Protein[1-40], Amyloid Precursor Protein, Beta Secretase, Glycogen Synthase Kinase 3beta, Insulin, Animal Cell, Article, Cell Fractionation, Controlled Study, Drug Effect, Embryo, Human, Human Cell, Immunofluorescence, In Vitro Study, Kidney Cell, Nerve Cell, Nonhuman, Nucleotide Sequence, Priority Journal, Protein Dephosphorylation, Protein Phosphorylation, Amyloid Beta-Protein Precursor, Amyloid Precursor Protein Secretases, Cell Line, Tumor, Cultured, Insulysin, Neurons, Signal Transduction, Amyloid Precursor Protein Secretases Metabolism, Amyloid Beta-Protein Precursor Metabolism, Glycogen Synthase Kinases Metabolism, Insulin Pharmacology, Insulysin Metabolism, Neurons Drug Effects Metabolism, Phosphorylation Drug Effects, Signal Transduction Drug Effects, Amyloid Beta Protein [1-40],
Affiliations: *** IBB - CNR ***
Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi-Nesima Hospital, Via Palermo 636, Catania 95122, Italy
Department of Drug Sciences, University of Catania, National Council of Research (Institute of Biostructures and Bioimages), Catania, 95125, Italy
References: Zheng, H., Koo, E.H., The amyloid precursor protein: Beyond amyloid (2006) Mol Neurodegener, 1, p.
Buoso, E., Lanni, C., Schettini, G., Govoni, S., Racchi, M., β-Amyloid precursor protein metabolism: Focus on the functions and degradation of its intracellular domain (2010) Pharmacol Res, 62, pp. 308-317
Zhang, H., Ma, Q., Zhang, Y.W., Xu, H., Proteolytic processing of Alzheimer's β-amyloid precursor protein (2012) J Neurochem, 120 (SUPPL. 1), pp. 9-21
Lee, M.-S., Kao, S.-C., Lemere, C.A., Xia, W., Tseng, H.-C., Zhou, Y., Neve, R., Tsai, L.-H., APP processing is regulated by cytoplasmic phosphorylation (2003) Journal of Cell Biology, 163 (1), pp. 83-95. , DOI 10.1083/jcb.200301115
Iijima, K.-I., Ando, K., Takeda, S., Satoh, Y., Seki, T., Itohara, S., Greengard, P., Suzuki, T., Neuron-specific phosphorylation of Alzheimer's β-amyloid precursor protein by cyclin-dependent kinase 5 (2000) Journal of Neurochemistry, 75 (3), pp. 1085-1091. , DOI 10.1046/j.1471-4159.2000.0751085.x
Ando, K., Oishi, M., Takeda, S., Iijima, K.-I., Lsohara, T., Nairn, A.C., Kirino, Y., Suzuki, T., Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation (1999) Journal of Neuroscience, 19 (11), pp. 4421-4427
Aplin, A.E., Gibb, G.M., Jacobsen, J.S., Gallo, J.-M., Anderton, B.H., In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3β (1996) Journal of Neurochemistry, 67 (2), pp. 699-707
Suzuki, T., Oishi, M., Marshak, D.R., Czernik, A.J., Nairn, A.C., Greengard, P., Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein (1994) EMBO Journal, 13 (5), pp. 1114-1122
Taru, H., Iijima, K.-I., Hase, M., Kirino, Y., Yagi, Y., Suzuki, T., Interaction of Alzheimer's β-amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade (2002) Journal of Biological Chemistry, 277 (22), pp. 20070-20078. , DOI 10.1074/jbc.M108372200
Cao, X., Sudhof, T.C., A transcriptivety active complex of APP with Fe65 and histone acetyltransferase Tip60 (2001) Science, 293 (5527), pp. 115-120. , DOI 10.1126/science.1058783
Chang, K.-A., Kim, H.-S., Ha, T.-Y., Ha, J.-W., Shin, K.Y., Jeong, Y.H., Lee, J.-P., Suh, Y.-H., Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration (2006) Molecular and Cellular Biology, 26 (11), pp. 4327-4338. , DOI 10.1128/MCB.02393-05
Von, R.R.C., Kohli, B.M., Bosset, J., Meier, M., Suzuki, T., Nitsch, R.M., Konietzko, U., The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor (2004) Journal of Cell Science, 117 (19), pp. 4435-4448. , DOI 10.1242/jcs.01323
Kinoshita, A., Whelan, C.M., Smith, C.J., Berezovska, O., Hyman, B.T., Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: Association with Fe65 and translocation to the nucleus (2002) J Neurochem, 82, pp. 839-847
Kim, H.-S., Kim, E.-M., Kim, N.-J., Chang, K.-A., Choi, Y., Ahn, K.-W., Lee, J.-H., Suh, Y.-H., Inhibition of Histone Deacetylation Enhances the Neurotoxicity Induced by the C-Terminal Fragments of Amyloid Precursor Protein (2004) Journal of Neuroscience Research, 75 (1), pp. 117-124. , DOI 10.1002/jnr.10845
Arvanitakis, Z., Wilson, R.S., Bienias, J.L., Evans, D.A., Bennett, D.A., Diabetes Mellitus and Risk of Alzheimer Disease and Decline in Cognitive Function (2004) Archives of Neurology, 61 (5), pp. 661-666. , DOI 10.1001/archneur.61.5.661
Grodstein, F., Chen, J., Wilson, R.S., Manson, J.E., Type 2 diabetes and cognitive function in community-dwelling elderly women (2001) Diabetes Care, 24 (6), pp. 1060-1065
Ott, A., Stolk, R.P., Van Harskamp, F., Pols, H.A., Hofman, A., Breteler, M.M., Diabetes mellitus and the risk of dementia: The Rotterdam Study (1999) Neurology, 53, pp. 1937-1942
Xu, W.L., Qiu, C.X., Wahlin, A., Winblad, B., Fratiglioni, L., Diabetes mellitus and risk of dementia in the Kungsholmen project: A 6-year follow-up study (2004) Neurology, 63 (7), pp. 1181-1186
Kodl, C.T., Seaquist, E.R., Cognitive dysfunction and diabetes mellitus (2008) Endocrine Reviews, 29 (4), pp. 494-511. , http://edrv.endojournals.org/cgi/reprint/29/4/494, DOI 10.1210/er.2007-0034
Leibson, C.L., Rocca, W.A., Hanson, V.A., Cha, R., Kokmen, E., O'Brien, P.C., Palumbo, P.J., Risk of dementia among persons with diabetes mellitus: A population- based cohort study (1997) American Journal of Epidemiology, 145 (4), pp. 301-308
Luchsinger, J.A., Tang, M.-X., Shea, S., Mayeux, R., Hyperinsulinemia and risk of Alzheimer disease (2004) Neurology, 63 (7), pp. 1187-1192
Craft, S., Peskind, E., Schwartz, M.W., Schellenberg, G.D., Raskind, M., Porte Jr., D., Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: Relationship to severity of dementia and apolipoprotein e genotype (1998) Neurology, 50, pp. 164-168
Reger, M.A., Watson, G.S., Green, P.S., Wilkinson, C.W., Baker, L.D., Cholerton, B., Fishel, M.A., Craft, S., Intranasal insulin improves cognition and modulates β-amyloid in early AD (2008) Neurology, 70, pp. 440-448
Shemesh, E., Rudich, A., Harman-Boehm, I., Cukierman-Yaffe, T., Effect of intranasal insulin on cognitive function: A systematic review (2012) J Clin Endocrinol Metab, 97, pp. 366-376
Craft, S., Baker, L.D., Montine, T.J., Minoshima, S., Watson, G.S., Claxton, A., Arbuckle, M., Gerton, B., Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: A pilot clinical trial (2012) Arch Neurol, 69, pp. 29-38
Zhao, W.-Q., Alkon, D.L., Role of insulin and insulin receptor in learning and memory (2001) Molecular and Cellular Endocrinology, 177 (1-2), pp. 125-134. , DOI 10.1016/S0303-7207(01)00455-5, PII S0303720701004555
Craft, S., Watson, G.S., Insulin and neurodegenerative disease: Shared and specific mechanisms (2004) Lancet Neurology, 3 (3), pp. 169-178. , DOI 10.1016/S1474-4422(04)00681-7
Copani, A., Condorelli, F., Caruso, A., Vancheri, C., Sala, A., Giuffrida Stella, A.M., Canonico, P.L., Sortino, M.A., Mitotic signaling by β-amyloid causes neuronal death (1999) FASEB J, 13, pp. 2225-2234
Pandini, G., Vigneri, R., Costantino, A., Frasca, F., Ippolito, A., Fujita-Yamaguchi, Y., Siddle, K., Belfiore, A., Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: Evidence for a second mechanism of IGF-I signaling (1999) Clinical Cancer Research, 5 (7), pp. 1935-1944
Belfiore, A., Frasca, F., Pandini, G., Sciacca, L., Vigneri, R., Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease (2009) Endocr Rev, 30, pp. 586-623
Ceresa, B.P., Pessin, J.E., Insulin regulation of the Ras activation/inactivation cycle (1998) Molecular and Cellular Biochemistry, 182 (1-2), pp. 23-29. , DOI 10.1023/A:1006819008507
De Meyts, P., Christoffersen, C.T., Ursø, B., Wallach, B., Gronskov, K., Yakushiji, F., Shymko, R.M., Role of the time factor in signaling specificity: Application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases (1995) Metabolism, 44, pp. 2-11
Suzuki, N., Cheung, T.T., Cai, X.D., Odaka, A., Otvos Jr., L., Eckman, C., Golde, T.E., Younkin, S.G., An increased percentage of long amyloid β protein secreted by familial amyloid β protein precursor (β APP717) mutants (1994) Science, 264, pp. 1336-1340
Solano, D.C., Sironi, M., Bonfini, C., Solerte, S.B., Govoni, S., Racchi, M., Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway (2000) FASEB Journal, 14 (7), pp. 1015-1022
Gasparini, L., Gouras, G.K., Wang, R., Gross, R.S., Beal, M.F., Greengard, P., Xu, H., Stimulation of β-amyloid precursor protein trafficking by insulin reduces intraneuronal β-amyloid and requires mitogen-activated protein kinase signaling (2001) Journal of Neuroscience, 21 (8), pp. 2561-2570
Kimberly, W.T., Zheng, J.B., Guénette, S.Y., Selkoe, D.J., The intracellular domain of the β-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner (2001) J Biol Chem, 276, pp. 40288-40292
Slomnicki, L.P., Lesniak, W., A putative role of the Amyloid Precursor Protein Intracellular Domain (AICD) in transcription (2008) Acta Neurobiologiae Experimentalis, 68 (2), pp. 219-228. , http://www.nencki.gov.pl/pdf/an/vol68/slomnicki.pdf
Edbauer, D., Willem, M., Lammich, S., Steiner, H., Haass, C., Insulin-degrading enzyme rapidly removes the β-amyloid precursor protein intracellular domain (AICD) (2002) Journal of Biological Chemistry, 277 (16), pp. 13389-13393. , DOI 10.1074/jbc.M111571200
Baker, L.D., Cross, D.J., Minoshima, S., Belongia, D., Watson, G.S., Craft, S., Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes (2011) Arch Neurol, 68, pp. 51-57
Riederer, P., Bartl, J., Laux, G., Grünblatt, E., Diabetes type II: A risk factor for depression-Parkinson-Alzheimer? (2011) Neurotox Res, 19, pp. 253-265
Peila, R., Rodriguez, B.L., Launer, L.J., Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study (2002) Diabetes, 51 (4), pp. 1256-1262
Park, S.A., A common pathogenic mechanism linking type-2 diabetes and Alzheimer's disease: Evidence from animal models (2011) J Clin Neurol, 7, pp. 10-18
Stohr, O., Schilbach, K., Moll, L., Hettich, M.M., Freude, S., Wunderlich, F.T., Ernst, M., Schubert, M., Insulin receptor signaling mediates APP processing and β-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer's disease (2011) Age, , 6. November 10.1007/s11357-011-9333-2
Picone, P., Giacomazza, D., Vetri, V., Carrotta, R., Militello, V., San Biagio, P.L., Di Carlo, M., Insulin-activated Akt rescues Aβ oxidative stress-induced cell death by orchestrating molecular trafficking (2011) Aging Cell, 10, pp. 832-843
Havrankova, J., Roth, J., Brownstein, M., Insulin receptors are widely distributed in the central nervous system of the rat (1978) Nature, 272 (5656), pp. 827-829. , DOI 10.1038/272827a0
Cross, D.A.E., Alessi, D.R., Cohen, P., Andjelkovich, M., Hemmings, B.A., Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B (1995) Nature, 378 (6559), pp. 785-789. , DOI 10.1038/378785a0
Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E.A., Frosch, M.P., Eckman, C.B., Guenette, S., Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo (2003) Proceedings of the National Academy of Sciences of the United States of America, 100 (7), pp. 4162-4167. , DOI 10.1073/pnas.0230450100
Vekrellis, K., Ye, Z., Qiu, W.Q., Walsh, D., Hartley, D., Chesneau, V., Rosner, M.R., Selkoe, D.J., Neurons regulate extracellular levels of amyloid β-protein via proteolysis by insulin-degrading enzyme (2000) Journal of Neuroscience, 20 (5), pp. 1657-1665
De La Monte, S.M., Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease (2012) Curr Alzheimer Res, 9, pp. 35-66
Zheng, H., Koo, E. H., The amyloid precursor protein: Beyond amyloid (2006) Mol Neurodegener, 1, p.
Lee, M. -S., Kao, S. -C., Lemere, C. A., Xia, W., Tseng, H. -C., Zhou, Y., Neve, R., Tsai, L. -H., APP processing is regulated by cytoplasmic phosphorylation (2003) Journal of Cell Biology, 163 (1), pp. 83-95. , DOI 10. 1083/jcb. 200301115
Iijima, K. -I., Ando, K., Takeda, S., Satoh, Y., Seki, T., Itohara, S., Greengard, P., Suzuki, T., Neuron-specific phosphorylation of Alzheimer's -amyloid precursor protein by cyclin-dependent kinase 5 (2000) Journal of Neurochemistry, 75 (3), pp. 1085-1091. , DOI 10. 1046/j. 1471-4159. 2000. 0751085. x
Aplin, A. E., Gibb, G. M., Jacobsen, J. S., Gallo, J. -M., Anderton, B. H., In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3 (1996) Journal of Neurochemistry, 67 (2), pp. 699-707
Chang, K. -A., Kim, H. -S., Ha, T. -Y., Ha, J. -W., Shin, K. Y., Jeong, Y. H., Lee, J. -P., Suh, Y. -H., Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration (2006) Molecular and Cellular Biology, 26 (11), pp. 4327-4338. , DOI 10. 1128/MCB. 02393-05
Von, R. R. C., Kohli, B. M., Bosset, J., Meier, M., Suzuki, T., Nitsch, R. M., Konietzko, U., The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor (2004) Journal of Cell Science, 117 (19), pp. 4435-4448. , DOI 10. 1242/jcs. 01323
Kim, H. -S., Kim, E. -M., Kim, N. -J., Chang, K. -A., Choi, Y., Ahn, K. -W., Lee, J. -H., Suh, Y. -H., Inhibition of Histone Deacetylation Enhances the Neurotoxicity Induced by the C-Terminal Fragments of Amyloid Precursor Protein (2004) Journal of Neuroscience Research, 75 (1), pp. 117-124. , DOI 10. 1002/jnr. 10845
Ott, A., Stolk, R. P., Van Harskamp, F., Pols, H. A., Hofman, A., Breteler, M. M., Diabetes mellitus and the risk of dementia: The Rotterdam Study (1999) Neurology, 53, pp. 1937-1942
Xu, W. L., Qiu, C. X., Wahlin, A., Winblad, B., Fratiglioni, L., Diabetes mellitus and risk of dementia in the Kungsholmen project: A 6-year follow-up study (2004) Neurology, 63 (7), pp. 1181-1186
Kodl, C. T., Seaquist, E. R., Cognitive dysfunction and diabetes mellitus (2008) Endocrine Reviews, 29 (4), pp. 494-511. , http: //edrv. endojournals. org/cgi/reprint/29/4/494, DOI 10. 1210/er. 2007-0034
Leibson, C. L., Rocca, W. A., Hanson, V. A., Cha, R., Kokmen, E., O'Brien, P. C., Palumbo, P. J., Risk of dementia among persons with diabetes mellitus: A population- based cohort study (1997) American Journal of Epidemiology, 145 (4), pp. 301-308
Luchsinger, J. A., Tang, M. -X., Shea, S., Mayeux, R., Hyperinsulinemia and risk of Alzheimer disease (2004) Neurology, 63 (7), pp. 1187-1192
Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Craft, S., Intranasal insulin improves cognition and modulates -amyloid in early AD (2008) Neurology, 70, pp. 440-448
Zhao, W. -Q., Alkon, D. L., Role of insulin and insulin receptor in learning and memory (2001) Molecular and Cellular Endocrinology, 177 (1-2), pp. 125-134. , DOI 10. 1016/S0303-7207 (01) 00455-5, PII S0303720701004555
Ceresa, B. P., Pessin, J. E., Insulin regulation of the Ras activation/inactivation cycle (1998) Molecular and Cellular Biochemistry, 182 (1-2), pp. 23-29. , DOI 10. 1023/A: 1006819008507
Solano, D. C., Sironi, M., Bonfini, C., Solerte, S. B., Govoni, S., Racchi, M., Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway (2000) FASEB Journal, 14 (7), pp. 1015-1022
Kimberly, W. T., Zheng, J. B., Gu nette, S. Y., Selkoe, D. J., The intracellular domain of the -amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner (2001) J Biol Chem, 276, pp. 40288-40292
Slomnicki, L. P., Lesniak, W., A putative role of the Amyloid Precursor Protein Intracellular Domain (AICD) in transcription (2008) Acta Neurobiologiae Experimentalis, 68 (2), pp. 219-228. , http: //www. nencki. gov. pl/pdf/an/vol68/slomnicki. pdf
Baker, L. D., Cross, D. J., Minoshima, S., Belongia, D., Watson, G. S., Craft, S., Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes (2011) Arch Neurol, 68, pp. 51-57
Park, S. A., A common pathogenic mechanism linking type-2 diabetes and Alzheimer's disease: Evidence from animal models (2011) J Clin Neurol, 7, pp. 10-18
Chua, L. M., Lim, M. L., Chong, P. R., Hu, Z. P., Cheung, N. S., Wong, B. S., Impaired neuronal insulin signaling precedes A42 accumulation in female A PPsw/PS1 E9 mice (2012) J Alzheimers Dis, 29, pp. 783-791
Zhao, W. Q., Lacor, P. N., Chen, H., Lambert, M. P., Quon, M. J., Krafft, G. A., Klein, W. L., Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric A (2009) J Biol Chem, 284, pp. 18742-18753
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., Hemmings, B. A., Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B (1995) Nature, 378 (6559), pp. 785-789. , DOI 10. 1038/378785a0
De La Monte, S. M., Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease (2012) Curr Alzheimer Res, 9, pp. 35-66
Insulin has multiple antiamyloidogenic effects on human neuronal cells