Abstract
Fibril formation by amyloidogenic proteins and peptides is considered the cause of a number of incurable diseases. One of the most known amyloid diseases is Alzheimer’s disease (AD). Traditionally, amyloidogenic beta peptides Aβ40 and Aβ42 (Aβs) are considered as main causes of AD and the foremost targets in AD fight. The main efforts in pharmacology are aimed at reducing Aβs concentration to prevent their accumulation, aggregation, formation of senile plaques, neuronal death, and neurodegeneration. However, a number of publications have demonstrated certain beneficial physiological effects of Aβs. Simultaneously, it is indicated that the effects of Aβs turn into pathological due to the development of certain diseases in the body. The accumulation of C- and N-terminal truncated Aβs under diverse conditions is supposed to play a role in AD development. The significance of transformation of glutamate residue at positions 3 or 11 of Aβs catalyzed by glutaminyl cyclase making them more degradation resistant, hydrophobic, and prone to aggregation, as well as the participation of dipeptidyl peptidase IV in these transformations are discussed. The experimental data presented confirm the maintenance of physiological, nonaggregated state of Aβs by plant preparations. In conclusion, this review suggests that in the fight against AD, instead of removing Aβs, preference should be given to the treatment of common diseases. Glutaminyl cyclase and dipeptidyl peptidase IV can be considered as targets in AD treatment. Flavonoids and plant preparations that possess antiamyloidogenic propensity are proposed as beneficial neuroprotective, anticancer, and antidiabetic food additives.
Funding source: the Ministry of Education and Science of the Republic of Armenia, Agreement No. 15
-
Research ethics: Not applicable.
-
Author contributions: SM contributed to the conception of principal idea, wrote the first draft of the manuscript. All authors contributed to the manuscript edition and approved the submitted version.
-
Competing interests: The authors declare no conflict of interest.
-
Research funding: This work was supported by the Ministry of Education and Science of the Republic of Armenia, Agreement No. 15.
-
Data availability: Not applicable.
References
Alves da Costa, C., Sunyach, C., Pardossi-Piquard, R., Sévalle, J., Vincent, B., Boyer, N., Kawarai, T., Girardot, N., George-Hyslop, P.St., and Checler, F. (2006). Presenilin-dependent gamma-secretase mediated control of p53-associated cell death in Alzheimer’s disease. J. Neurosci. 26: 6377–6385, https://doi.org/10.1523/jneurosci.0651-06.2006.Search in Google Scholar PubMed PubMed Central
Antonyan, A.A., Sharoyan, S.G., Harutyunyan, H.A., and Mardanyan, S.S. (2009). Influence of aluminum toxicosis on the activity of adenosine deaminase and dipeptidyl peptidases II and IV. Neurochem. J. 3: 118–121, https://doi.org/10.1134/s181971240902007x.Search in Google Scholar
Antonyan, A., Sharoyan, S., Harutyunyan, H., Barboni, L., Lupidi, G., and Mardanyan, S. (2016). Protection of hippocampal and islet β cells in vitro by emodin from leaves of Rumex confertus. Int. J. Pharmacogn. 3: 437–444.Search in Google Scholar
Antonyan, A., Schlenzig, D., Schilling, S., Naumann, M., Sharoyan, S., Mardanyan, S., and Demuth, H.-U. (2018). Concerted action of dipeptidyl peptidase IV and glutaminylcyclase results in formation of pyroglutamate-modified amyloid peptides in vitro. Neurochem. Int. 113: 112–119, https://doi.org/10.1016/j.neuint.2017.12.001.Search in Google Scholar PubMed
Armstrong, R.A. (2011). The pathogenesis of Alzheimer’s disease: a reevaluation of the “amyloid cascade hypothesis”. Int. J. Alzheimer’s Dis. 2011: 630865, https://doi.org/10.4061/2011/630865.Search in Google Scholar PubMed PubMed Central
Atwood, C.S., Bishop, G.M., Perry, G., and Smith, M.A. (2002). Amyloid-beta: a vascular sealant that protects against hemorrhage? J. Neurosci. Res. 70: 356, https://doi.org/10.1002/jnr.10388.Search in Google Scholar PubMed
Atwood, C.S., Bowen, R.L., Smith, M.A., and Perry, G. (2003). Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply. Brain Res. Rev. 43: 164–178, https://doi.org/10.1016/s0165-0173(03)00206-6.Search in Google Scholar PubMed
Bader, A.S., Gnädig, M.U., Fricke, M., Büschgens, L., Berger, L.J., Klafki, H.W., Meyer, T., Jahn, O., Weggen, S., and Wirths, O. (2023). Brain region-specific differences in amyloid-β plaque composition in 5XFAD mice. Life 13: 1053, https://doi.org/10.3390/life13041053.Search in Google Scholar PubMed PubMed Central
Bayer, T.A. (2022). Pyroglutamate Aβ cascade as drug target in Alzheimer’s disease. Mol. Psychiatry 27: 880–1885, https://doi.org/10.1038/s41380-021-01409-2.Search in Google Scholar PubMed PubMed Central
Bernabeu-Zornoza, A., Coronel, R., Palmer, C., Martín, A., López-Alonso, V., and Liste, I. (2022). Neurogenesis is increased in human neural stem cells by Aβ40 peptide. Int. J. Mol. Sci. 23: 5820, https://doi.org/10.3390/ijms23105820.Search in Google Scholar PubMed PubMed Central
Bernstein, H.G., Schön, E., Ansorge, S., Röse, I., and Dorn, A. (1987). Immunolocalization of dipeptidyl aminopeptidase (dap iv) in the developing human brain. Int. J. Dev. Neurosci. 5: 237–242, https://doi.org/10.1016/0736-5748(87)90034-7.Search in Google Scholar PubMed
Bernstein, H.-G., Dobrowolny, H., Keilhoff, G., and Steiner, J. (2018). Dipeptidyl peptidase IV, which probably plays important roles in Alzheimer disease (AD) pathology, is upregulated in AD brain neurons and associates with amyloid plaques. Neurochem. Int. 114: 55–57, https://doi.org/10.1016/j.neuint.2018.01.005.Search in Google Scholar PubMed
Bernstein, H.-G., Keilhoff, G., Dobrowolny, H., and Steiner, J. (2022). The many facets of CD26/dipeptidyl peptidase 4 and its inhibitors in disorders of the CNS – a critical overview. Rev. Neurosci. 34: 1–24, https://doi.org/10.1515/revneuro-2022-0026.Search in Google Scholar PubMed
Berntsson, E., Vosough, F., Svantesson, T., Pansieri, J., Iashchishyn, I.A., Ostojić, L., Dong, X., Paul, S., Jarvet, J., Roos, P.M., et al.. (2023). Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides. Sci. Rep. 13: 3341, https://doi.org/10.1038/s41598-023-29901-5.Search in Google Scholar PubMed PubMed Central
Biron, K.E., Dickstein, D.L., Gopaul, R., and Jefferies, W.A. (2011). Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer’s disease. PLoS One 6: e23789, https://doi.org/10.1371/journal.pone.0023789.Search in Google Scholar PubMed PubMed Central
Bourgade, K., Garneau, H., Giroux, G., Le Page, A.Y., Bocti, C., Dupuis, G., Frost, E.H., and Fülöp, T.Jr. (2015). β-Amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1. Biogerontology 16: 85–98, https://doi.org/10.1007/s10522-014-9538-8.Search in Google Scholar PubMed
Brothers, H.M., Gosztyla, M.L., and Robinson, S.R. (2018). The physiological roles of amyloid-β peptide hint at new ways to treat Alzheimer’s disease. Front Aging Neurosci 10: 118, https://doi.org/10.3389/fnagi.2018.00118.Search in Google Scholar PubMed PubMed Central
Busek, P., Stremenova, J., Sromova, L., Hilser, M., Balaziova, E., Kosek, D., Trylcova, J., Strnad, H., Krepela, E., and Sedo, A. (2012). Dipeptidyl peptidase-IV inhibits glioma cell growth independent of its enzymatic activity. Int. J. Biochem. Cell Biol. 44: 738–747, https://doi.org/10.1016/j.biocel.2012.01.011.Search in Google Scholar PubMed
Cai, W., Li, L., Sang, S., Pan, X., and Zhong, C. (2023). Physiological roles of β-amyloid in regulating synaptic function: implications for AD pathophysiology. Neurosci. Bull. 39: 1289–1308, https://doi.org/10.1007/s12264-022-00985-9.Search in Google Scholar PubMed PubMed Central
Calderaro, A., Patanè, G.T., Tellone, E., Barreca, D., Ficarra, S., Misiti, F., and Laganà, G. (2022). The neuroprotective potentiality of flavonoids on Alzheimer’s disease. Int. J. Mol. Sci. 23: 14835, https://doi.org/10.3390/ijms232314835.Search in Google Scholar PubMed PubMed Central
Carrillo-Mora, P., Luna, R., and Colín-Barenque, L. (2014). Amyloid beta: multiple mechanisms of toxicity and only some protective effects? Oxidat. Med. Cell Longev. 2014: 795375, https://doi.org/10.1155/2014/795375.Search in Google Scholar PubMed PubMed Central
Coronel, R., Bernabeu-Zornoza, A., Palmer, C., González-Sastre, R., Rosca, A., Mateos-Martínez, P., López-Alonso, V., and Liste, I. (2023). Amyloid precursor protein (APP) regulates gliogenesis and neurogenesis of human neural stem cells by several signaling pathways. Int. J. Mol. Sci. 24: 12964, https://doi.org/10.3390/ijms241612964.Search in Google Scholar PubMed PubMed Central
Cummings, J., Aisen, P., Apostolova, L.G., Atri, A., Salloway, S., and Weiner, M. (2021). Aducanumab: appropriate use recommendations. J. Prev. Alzheimers Dis. 8: 398–410.Search in Google Scholar
Cummings, J., Rabinovici, G.D., Atri, A., Aisen, P., Apostolova, L.G., Hendrix, S., Sabbagh, M., Selkoe, D., Weiner, M., and Salloway, S., and Alzheimer’s Disease and Related Disorders Therapeutics Working Group (2022). Aducanumab: appropriate use recommendations update. J. Prev. Alzheimers Dis. 9: 221–230, https://doi.org/10.14283/jpad.2022.34.Search in Google Scholar PubMed PubMed Central
Cynis, H., Scheel, E., Saido, T.C., Schilling, S., and Demuth, H.U. (2008). Amyloidogenic processing of amyloid precursor protein: evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-β. Biochemistry 47: 7405–7413, https://doi.org/10.1021/bi800250p.Search in Google Scholar PubMed
D’Amico, M., Di Filippo, C., Marfella, R., Abbatecola, A.M., Ferraraccio, F., Rossi, F., and Paolisso, G. (2010). Long-term inhibition of dipeptidyl peptidase-4 in Alzheimer’s prone mice. Exp. Gerontol. 45: 202–207, https://doi.org/10.1016/j.exger.2009.12.004.Search in Google Scholar PubMed
Dammers, C., Gremer, L., Reiß, K., Klein, A.N., Neudecker, P., Hartmann, R., Sun, N., Demuth, H.-U., Schwarten, M., and Willbold, D. (2015). Structural analysis and aggregation propensity of pyroglutamate Aβ(3-40) in aqueous trifluoroethanol. PLoS One 10: e0143647, https://doi.org/10.1371/journal.pone.0143647.Search in Google Scholar PubMed PubMed Central
de Souza, I.D. and Queiroz, M.E.C. (2023). Advances in sample preparation and HPLC-MS/MS methods for determining amyloid-β peptide in biological samples: a review. Anal. Bioanal. Chem. 415: 4003–4021, https://doi.org/10.1007/s00216-023-04631-9.Search in Google Scholar PubMed
Del Carmen, S.M., Laura, G.V., Leonardo, O.L., Bernabé, R.G., and Antonio, M.M. (2020). Aβ40 oligomers promote survival and early neuronal differentiation of dentate gyrus-isolated precursor cells through activation of the Akt signaling pathway. Neurotox Res. 38: 611–625, https://doi.org/10.1007/s12640-020-00253-6.Search in Google Scholar PubMed
Eimer, W.A., Vijaya Kumar, D.K., Navalpur Shanmugam, N.K., Rodriguez, A.S., Mitchell, T., Washicosky, K.J., György, B., Breakefield, X.O., Tanzi, R.E., and Moir, R.D. (2018). Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpes-viridae to protect against brain infection. Neuron 99: 56–63.e3, https://doi.org/10.1016/j.neuron.2018.06.030.Search in Google Scholar PubMed PubMed Central
Fagiani, F., Lanni, C., Marco, R., Alessia, P., and Stefano, G. (2019). Amyloid-β and synaptic vesicle dynamics: a cacophonic orchestra. J. Alzheimer’s Dis. 72: 1–14, https://doi.org/10.3233/jad-190771.Search in Google Scholar PubMed
Fisher, R.A., Miners, J.S., and Love, S. (2022). Pathological changes within the cerebral vasculature in Alzheimer’s disease: new perspectives. Brain Pathol 32: e13061, https://doi.org/10.1111/bpa.13061.Search in Google Scholar PubMed PubMed Central
Galanis, C., Fellenz, M., Becker, D., Bold, C., Lichtenthaler, S.F., Müller, U.C., Deller, T., and Vlachos, A. (2021). Amyloid-beta mediates homeostatic synaptic plasticity. J. Neurosci. 41: 5157–5172, https://doi.org/10.1523/jneurosci.1820-20.2021.Search in Google Scholar PubMed PubMed Central
Grant, J.L., Ghosn, E.E., Axtell, R.C., Herges, K., Kuipers, H.F., Woodling, N.S., Andreasson, K., Herzenberg, L.A., Herzenberg, L.A., and Steinman, L. (2012). Reversal of paralysis and reduced inflammation from peripheral administration of β-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis. Sci. Transl. Med. 4: 145ra105, https://doi.org/10.1126/scitranslmed.3004145.Search in Google Scholar PubMed PubMed Central
Hartlage-Rübsamen, M., Morawski, M., Waniek, A., Jäger, C., Zeitschel, U., Koch, B., Cynis, H., Schilling, S., Schliebs, R., Demuth, H.U., et al.. (2011). Glutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Aβ deposits in hippocampus via distinct cellular mechanisms. Acta Neuropathol. 121: 705–719, https://doi.org/10.1007/s00401-011-0806-2.Search in Google Scholar PubMed PubMed Central
Harutyunyan, H., Sharoyan, S., Antonyan, A., and Mardanyan, S. (2017a). Herb preparations improve the viability of hippocampal cells suppressed by amyloid beta (1-42) peptide. World J. Pharm. Sci. 5: 207–212.Search in Google Scholar
Harutyunyan, H., Sharoyan, S., Antonyan, A., and Mardanyan, S. (2017b). Herbal preparations prevent Aβ peptides induced hippocampal cell damage. Intern. J. Herb Med. 5: 92–105.Search in Google Scholar
Hoffmann, T., Meyer, A., Heiser, U., Kurat, S., Böhme, L., Kleinschmidt, M., Bühring, K.-U., Hutter-Paier, B., Farcher, M., Demuth, H.-U., et al.. (2017). Glutaminyl cyclase inhibitor PQ912 improves cognition in mouse models of Alzheimer’s disease – studies on relation to effective target occupancy. J. Pharmacol. Exp. Ther. 362: 119–130, https://doi.org/10.1124/jpet.117.240614.Search in Google Scholar PubMed
Hovnanyan, K., Sharoyan, S., Antonyan, A., and Mardanyan, S. (2017). Influence of extract and phenol glycosides from rose petals on the fibrils of amyloid peptide Aβ(1-42). Study by transmission electron microscopy. Proc. YSU Chem. Biol. 3: 203–208.10.4236/oalib.1103343Search in Google Scholar
Hu, Z.-W., Cruceta, L., Zhang, V., Sun, Y., and Qiang, W. (2021). Cross-seeded fibrillation induced by pyroglutamate-3 and truncated Aβ40 variants leads to Aβ40 structural polymorphism modulation and elevated toxicity. ACS Chem. Neurosci. 19: 3625–3637, https://doi.org/10.1021/acschemneuro.1c00341.Search in Google Scholar PubMed
Huang, J., Huang, N., Mao, Q., Shi, J., and Qiu, Y. (2023). Natural bioactive compounds in Alzheimer’s disease: from the perspective of type 3 diabetes mellitus. Front. Aging Neurosci. 15: 1130253, https://doi.org/10.3389/fnagi.2023.1130253.Search in Google Scholar PubMed PubMed Central
Huang, L.-K., Kuan, Y.-C., Lin, H.-W., and Hu, C.-J. (2023). Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update. J. Biomed. Sci. 30: 83, https://doi.org/10.1186/s12929-023-00976-6.Search in Google Scholar PubMed PubMed Central
Ikegawa, M., Kakuda, N., Miyasaka, T., Toyama, Y., Nirasawa, T., Minta, K., and Hanrieder, J. (2023). Mass spectrometry imaging in Alzheimer’s disease. Brain Connect. 13: 319–333, https://doi.org/10.1089/brain.2022.0057.Search in Google Scholar PubMed PubMed Central
Inyushin, M., Zayas-Santiago, A., Rojas, L., and Kucheryavykh, L. (2020). On the role of platelet-generated amyloid beta peptides in certain amyloidosis health complications. Front. Immunol. 11: 571083, https://doi.org/10.3389/fimmu.2020.571083.Search in Google Scholar PubMed PubMed Central
Jazvinscak Jembrek, M., Slade, N., Hof, P.R., and Simic, G. (2018). The interactions of p53 with tau and Aβ as potential therapeutic targets for Alzheimer’s disease. Prog. Neurobiol. 168: 104–127, https://doi.org/10.1016/j.pneurobio.2018.05.001.Search in Google Scholar PubMed
Jefferies, W.A., Price, K.A., Biron, K.E., Fenninger, F., Pfeifer, C.G., and Dickstein, D.L. (2013). Adjusting the compass: new insights into the role of angiogenesis in Alzheimer’s disease. Alzheimers Res. Ther. 5: 146–148, https://doi.org/10.1186/alzrt230.Search in Google Scholar PubMed PubMed Central
Jeong, H., Shin, H., Hong, S., and Kim, Y.S. (2022). Physiological roles of monomeric amyloid-β and implications for Alzheimer’s disease. Therapeutics Exp. Neurobiol. 31: 65–88, https://doi.org/10.5607/en22004.Search in Google Scholar PubMed PubMed Central
Kagan, B.L., Jang, H., Capone, R., Teran Arce, F., Ramachandran, S., Lal, R., and Nussinov, R. (2012). Antimicrobial properties of amyloid peptides. Mol. Pharm. 9: 708–717, https://doi.org/10.1021/mp200419b.Search in Google Scholar PubMed PubMed Central
Karisetty, B.C., Bhatnagar, A., Armour, E.M., Beaver, M., Zhang, H., and Elefant, F. (2020). Amyloid-b peptide impact on synaptic function and neuroepigenetic gene control reveal new therapeutic strategies for AD. Front. Mol. Neurosci. 13: 577622, https://doi.org/10.3389/fnmol.2020.577622.Search in Google Scholar PubMed PubMed Central
Kornelius, E., Lin, C.L., Chang, H.H., Li, H.H., Huang, W.N., Yang, Y.S., Lu, Y.L., Peng, C.H., and Huang, C.N. (2015). DPP-4 inhibitor linagliptin attenuates Aβ-induced cytotoxicity through activation of AMPK in neuronal cells. CNS Neurosci. Ther. 21: 549–557, https://doi.org/10.1111/cns.12404.Search in Google Scholar PubMed PubMed Central
Korovesis, D., Rubio-Tomás, T., and Tavernarakis, N. (2023). Oxidative stress in age-related neurodegenerative diseases: an overview of recent tools and findings. Antioxidants 12: 131, https://doi.org/10.3390/antiox12010131.Search in Google Scholar PubMed PubMed Central
Kosaraju, J., Murthy, V., Khatwal, R.B., Dubala, A., Chinni, S., Muthureddi Nataraj, S.K., and Basavan, D. (2013). Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer´s disease. J. Pharm. Pharmacol. 65: 1773–1784, https://doi.org/10.1111/jphp.12148.Search in Google Scholar PubMed
Kumar, D.K., Choi, S.H., Washicosky, K.J., Eimer, W.A., Tucker, S., Ghofrani, J., Lefkowitz, A., McColl, G., Goldstein, L.E., Tanzi, R.E., et al.. (2017). Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci. Transl. Med. 8: 340ra72, https://doi.org/10.1126/scitranslmed.aaf1059.Search in Google Scholar PubMed PubMed Central
Kumar, S., Gautam, V., Singh, B.P., and Kumar, D. (2023). Editorial: investigating the impact of bioactive metabolites and extracts in human health and disease. Front. Mol. Biosci. 10: 1244316, https://doi.org/10.3389/fmolb.2023.1244316.Search in Google Scholar PubMed PubMed Central
Kummer, M.P. and Heneka, M.T. (2014). Truncated and modified amyloid-beta species. Alzheimers Res. Ther. 6: 28, https://doi.org/10.1186/alzrt258.Search in Google Scholar PubMed PubMed Central
Liao, M.Q., Tzeng, Y.J., Chang, L.Y.X., Huang, H.B., Lin, T.H., Chyan, C.L., and Chen, Y.C. (2007). The correlation between neurotoxicity, aggregative ability and secondary structure studied by sequence truncated Ab peptides. FEBS Lett. 581: 1161–1165, https://doi.org/10.1016/j.febslet.2007.02.026.Search in Google Scholar PubMed
Liu, K., Solano, I., Mann, D., Lemere, C., Mercken, M., Trojanowski, J.Q., and Lee, V.M.Y. (2006). Characterization of Aß11-40/42 peptide deposition in Alzheimer’s disease and young Down’s syndrome brains: implication of N-terminally truncated Aß species in the pathogenesis of Alzheimer’s disease. Acta Neuropathol 112: 163–174, https://doi.org/10.1007/s00401-006-0077-5.Search in Google Scholar PubMed
Liu, Y., Shi, Y., and Wang, P. (2023). Functions of glutaminyl cyclase and its isoform in diseases. Visualized Cancer Med. 4: 1, https://doi.org/10.1051/vcm/2022008.Search in Google Scholar
Loeffler, D.A. (2023). Experimental approaches for altering the expression of Abeta-degrading enzymes. J. Neurochem. 164: 725–763, https://doi.org/10.1111/jnc.15762.Search in Google Scholar PubMed
Lukiw, W.J., Cui, J.G., Yuan, L.Y., Bhattacharjee, P.S., Corkern, M., Clement, C., Kammerman, E.M., Ball, M.J., Zhao, Y., Sullivan, P.M., et al.. (2010). Acyclovir or Aβ42 peptides attenuate HSV1-induced miRNA-146a levels in human primary brain cells. Neuroreport 21: 922–927, https://doi.org/10.1097/wnr.0b013e32833da51a.Search in Google Scholar
Maitra, S., Sornjai, W., Smith, D., and Vincent, B. (2021). Phenanthroline impairs βAPP processing and expression, increases p53 protein levels and induces cell cycle arrest in human neuroblastoma cells. Brain Res. Bull. 170: 29–38, https://doi.org/10.1016/j.brainresbull.2021.02.001.Search in Google Scholar PubMed
Masi, M., Biundo, F., Fiou, A., Racchi, M., Pascale, A., and Buoso, E. (2023). The labyrinthine landscape of APP processing: state of the art and possible novel soluble APP-related molecular players in traumatic brain injury and neurodegeneration. Int. J. Mol. Sci. 24: 6639, https://doi.org/10.3390/ijms24076639.Search in Google Scholar PubMed PubMed Central
Matos, J.O., Goldblatt, G., Jeon, J., Chen, B., and Tatulian, S.A. (2014). Pyroglutamylated amyloid-β peptide reverses cross β-sheets by a prion-like mechanism. J. Phys. Chem. B 118: 5637–5643, https://doi.org/10.1021/jp412743s.Search in Google Scholar PubMed PubMed Central
Moir, R.D., Lathe, R., and Tanzi, R.E. (2018). The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimers Dement. 14: 1602–1614, https://doi.org/10.1016/j.jalz.2018.06.3040.Search in Google Scholar PubMed
Mondello, S., Buki, A., Barzo, P., Randall, J., Provuncher, G., Hanlon, D., Wilson, D., Kobeissy, F., and Jeromin, A. (2014). CSF and plasma amyloid-β temporal profiles and relationships with neurological status and mortality after severe traumatic brain injury. Sci. Rep. 4: 6446, https://doi.org/10.1038/srep06446.Search in Google Scholar PubMed PubMed Central
Morató, X., Pytel, V., Jofresa, S., Ruiz, A., and Boada, M. (2022). Symptomatic and disease-modifying therapy pipeline for Alzheimer’s disease: towards a personalized polypharmacology patient-centered approach. Int. J. Mol. Sci. 23: 9305, https://doi.org/10.3390/ijms23169305.Search in Google Scholar PubMed PubMed Central
Morawski, M., Schilling, S., Kreuzberger, M., Waniek, A., Jäger, C., Koch, B., Cynis, H., Kehlen, A., Arendt, T., Hartlage-Rübsamen, M., et al.. (2014). Glutaminyl cyclase in human cortex: correlation with (pGlu)-amyloid-β load and cognitive decline in Alzheimer’s disease. J. Alzheimers Dis. 39: 385–400, https://doi.org/10.3233/jad-131535.Search in Google Scholar
Mori, H., Takio, K., Ogawara, M., and Selkoe, D.J. (1992). Mass spectrometry of purified amyloid beta protein in Alzheimer’s disease. J. Biol. Chem. 267: 17082–17086, https://doi.org/10.1016/s0021-9258(18)41896-0.Search in Google Scholar
Morley, J.E., Farr, S.A., Nguyen, A.D., and Xu, F. (2019). What is the physiological function of amyloid-beta protein? J. Nutr. Health Aging 23: 225–226, https://doi.org/10.1007/s12603-019-1162-5.Search in Google Scholar PubMed
Movsisyan, N.M., Sharoyan, S.G., Antonyan, A.A., and Mardanyan, S.S. (2013). Breakdown of some neuronal peptides with dipeptidyl peptidase IV. Proc. YSU Chem. Biol. 1: 36–39.Search in Google Scholar
Murariu, M., Habasescu, L., Ciobanu, C.-I., Gradinaru, R.V., Pui, A., Drochioiu, G., and Mangalagiu, I. (2019). Interaction of amyloid Aβ(9–16) peptide fragment with metal ions: CD, FT-IR, and fluorescence spectroscopic studies. Int. J. Peptide Res. Ther. 25: 897–909, https://doi.org/10.1007/s10989-018-9738-1.Search in Google Scholar
Nussbaum, J.M., Schilling, S., Cynis, H., Silva, A., Swanson, E., Wangsanut, T., Tayler, K., Wiltgen, B., Hatami, A., Rönicke, R., et al.. (2012). Prion-like behavior and tau-dependent cytotoxicity of pyroglutamylated β-amyloid. Nature 485: 651–655, https://doi.org/10.1038/nature11060.Search in Google Scholar PubMed PubMed Central
Ospina-Romero, M., Glymour, M.M., Hayes-Larson, E., Mayeda, E.R., Graff, R.E., Brenowitz, W.D., Ackley, S.F., Witte, J.S., and Kobayashi, L.C. (2020). Association between Alzheimer disease and cancer with evaluation of study biases: a systematic review and meta-analysis. JAMA Netw. Open 3: e2025515, https://doi.org/10.1001/jamanetworkopen.2020.25515.Search in Google Scholar PubMed PubMed Central
Pajoohesh-Ganji, A., Burns, M.P., Pal-Ghosh, S., Tadvalkar, G., Hokenbury, N.G., Stepp, M.A., and Faden, A.I. (2014). Inhibition of amyloid precursor protein secretases reduces recovery after spinal cord injury. Brain Res. 1560: 73–82, https://doi.org/10.1016/j.brainres.2014.02.049.Search in Google Scholar PubMed PubMed Central
Paris, D., Ganey, N., Banasiak, M., Laporte, V., Patel, N., Mullan, M., Murphy, S.F., Yee, G.T., Bachmeier, C., Ganey, C., et al.. (2010). Impaired orthotopic glioma growth and vascularization in transgenic mouse models of Alzheimer’s disease. J. Neurosci. 30: 11251–11258, https://doi.org/10.1523/jneurosci.2586-10.2010.Search in Google Scholar PubMed PubMed Central
Perez-Garmendia, R. and Gevorkian, G. (2013). Pyroglutamate-Modified amyloid beta peptides: emerging targets for Alzheimer’s disease immunotherapy. Curr. Neuropharmacol. 11: 491–498, https://doi.org/10.2174/1570159x11311050004.Search in Google Scholar
Perez-Garmendia, R., Hernandez-Zimbron, L.F., Morales, M.A., Luna-Muñoz, J., Mena, R., Nava-Catorce, M., Acero, G., Vasilevko, V., Viramontes-Pintos, A., Cribbs, D.H., et al.. (2014). Identification of N-terminally truncated pyroglutamate amyloid-β in cholesterol-enriched diet-fed rabbit and AD brain. J. Alzheimer’s Dis. 39: 441–455, https://doi.org/10.3233/jad-130590.Search in Google Scholar PubMed
Piccini, A., Russo, C., Gliozzi, A., Relini, A., Vitali, A., Borghi, R., Giliberto, L., Armirotti, A., D’Arrigo, C., Bachi, A., et al.. (2005). β-Amyloid is different in normal aging and in Alzheimer disease. J. Biol. Chem. 280: 34186–34192, https://doi.org/10.1074/jbc.m501694200.Search in Google Scholar PubMed
Pluta, R., Miziak, B., and Czuczwar, S.J. (2023). Post-ischemic permeability of the blood–brain barrier to amyloid and platelets as a factor in the maturation of Alzheimer’s disease-type brain neurodegeneration. Int. J. Mol. Sci. 24: 10739, https://doi.org/10.3390/ijms241310739.Search in Google Scholar PubMed PubMed Central
Portelius, E., Bogdanovic, N., Gustavsson, M.K., Volkmann, I., Brinkmalm, G., Zetterberg, H., Winblad, B., and Blennow, K. (2010). Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer’s disease. Acta Neuropathol. 120: 185–193, https://doi.org/10.1007/s00401-010-0690-1.Search in Google Scholar PubMed PubMed Central
Ristori, E., Donnini, S., and Ziche, M. (2020). New insights into blood-brain barrier aintenance: the homeostatic role of β-amyloid precursor protein in cerebral vasculature. Front. Physiol. 11: 1056, https://doi.org/10.3389/fphys.2020.01056.Search in Google Scholar PubMed PubMed Central
Robinson, S.R. and Bishop, G.M. (2002). Abeta as a bioflocculant: implications for the amyloid hypothesis of Alzheimer’s disease. Neurobiol. Aging 23: 1051–1072, https://doi.org/10.1016/s0197-4580(01)00342-6.Search in Google Scholar PubMed
Röhnert, P., Schmidt, W., Emmerlich, P., Goihl, A., Wrenger, S., Bank, U., Nordhoff, K., Täger, M., Ansorge, S., Reinhold, D., et al.. (2012). Dipeptidyl peptidase IV, aminopeptidase N and DPIV/APN-like proteases in cerebral ischemia. J. Neuroinflamm. 9: 44, https://doi.org/10.1186/1742-2094-9-44.Search in Google Scholar PubMed PubMed Central
Scheltens, P., Hallikainen, M., Grimmer, T., Duning, T., Gouw, A.A., Teunissen, C.E., Wink, A.M., Maruff, P., Harrison, J., Van Baal, C.M., et al.. (2018). Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled phase 2a study. Alzheimer’s Res. Ther. 10: 107, https://doi.org/10.1186/s13195-018-0431-6.Search in Google Scholar PubMed PubMed Central
Schilling, S., Hoffman, T., Manhart, S., Hoffman, and Demuth, H.-U. (2004). Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions. FEBS Lett. 563: 191–196, https://doi.org/10.1016/s0014-5793(04)00300-x.Search in Google Scholar PubMed
Schreiner, T.G., Schreiner, O.D., Adam, M., and Popescu, B.O. (2023). The roles of the amyloid β monomers in physiological and pathological conditions. Biomedicines 11: 1411, https://doi.org/10.3390/biomedicines11051411.Search in Google Scholar PubMed PubMed Central
Sehar, U., Rawat, P., Reddy, A.P., Kopel, J., and Reddy, P.H. (2022). Amyloid beta in aging and Alzheimer’s disease. Int. J. Mol. Sci. 23: 12924, https://doi.org/10.3390/ijms232112924.Search in Google Scholar PubMed PubMed Central
Sharoyan, S., Antonyan, A., Mardanyan, S., Harutyunyan, H., Movsisyan, N., Hovnanyan, N., and Hovnanyan, K. (2013). Interaction of dipeptidyl peptidase IV with amyloid peptides. Neurochem. Int. 62: 1048–1054, https://doi.org/10.1016/j.neuint.2013.03.017.Search in Google Scholar PubMed
Sharoyan, S., Antonyan, A., Harutyunyan, H., and Mardanyan, S. (2015). Plant preparations suppress the aggregation of amyloid beta peptides and promote their disaggregation. Proc. YSU Chem. Biol. 3: 40–46.Search in Google Scholar
Shirotani, K., Tsubuki, S., Lee, H.J., Maruyama, K., and Saido, T.C. (2002). Generation of amyloid beta peptide with pyroglutamate at position 3 in primary cortical neurons. Neurosci. Lett. 327: 25–28, https://doi.org/10.1016/s0304-3940(02)00351-8.Search in Google Scholar PubMed
Sinha, M., Bhowmick, P., Banerjee, A., and Chakrabarti, S. (2013). Antioxidant role of amyloid β protein in cell-free and biological systems: implication for the pathogenesis of Alzheimer disease. Free Radic. Biol. Med. 56: 184–192, https://doi.org/10.1016/j.freeradbiomed.2012.09.036.Search in Google Scholar PubMed
Soscia, S.J., Kirby, J.E., Washicosky, K.J., Tucker, S.M., Ingelsson, M., Hyman, B., Burton, M.A., Goldstein, L.E., Duong, S., Tanzi, R.E., et al.. (2010). The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 5: e9505, https://doi.org/10.1371/journal.pone.0009505.Search in Google Scholar PubMed PubMed Central
Spitzer, P., Condic, M., Herrmann, M., Oberstein, T.J., Scharin-Mehlmann, M., Gilbert, D.F., Friedrich, O., Grömer, T., Kornhuber, J., Lang, R., et al.. (2016). Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity. Sci. Rep. 6: 32228, https://doi.org/10.1038/srep32228.Search in Google Scholar PubMed PubMed Central
Stremenova, J., Krepela, E., Mares, V., Trim, J., Dbaly, V., Marek, J., Vanickova, Z., Lisa, V., Yea, C., and Sedo, A. (2007). Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade. Int. J. Oncol. 31: 785–792, https://doi.org/10.3892/ijo.31.4.785.Search in Google Scholar
Stremenová, J., Mares, V., Lisá, V., Hilser, M., Krepela, E., Vanicková, Z., Syrucek, M., Soula, O., and Sedo, A. (2010). Expression of dipeptidyl peptidase-IV activity and/or structure homologs in human meningiomas. Int. J. Oncol. 36: 351–358, https://doi.org/10.3892/ijo_00000506.Search in Google Scholar
Sturchio, A., Dwivedi, A.K., Malm, T., Wood, M.J.A., Cilia, R., Sharma, J.S., Hill, E.J., Schneider, L.S., Graff-Radford, N.R., Mori, H., et al.. (2022). Dominantly inherited Alzheimer consortia (DIAN) high soluble amyloid-β42 predicts normal cognition in amyloid-positive individuals with Alzheimer’s disease-causing mutations. J. Alzheimers Dis. 90: 333–348, https://doi.org/10.3233/jad-220808.Search in Google Scholar
van Dyck, C.H., Swanson, C.J., Aisen, P., Bateman, R.J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al.. (2023). Lecanemab in early Alzheimer’s disease. N. Engl. J. Med. 388: 9–21, https://doi.org/10.1056/nejmoa2212948.Search in Google Scholar PubMed
Vijverberg, E.G.B., Axelsen, T.M., Bihlet, A.R., Henriksen, K., Weber, F., Fuchs, K., Harrison, J.E., Kühn-Wache, K., Alexandersen, P., Prins, N.D., et al.. (2021). Rationale and study design of a randomized, placebo-controlled, double blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD–VIVIAD. Alzheimer’s Res. Ther. 13: 142, https://doi.org/10.1186/s13195-021-00882-9.Search in Google Scholar PubMed PubMed Central
Vojtechova, I., Machacek, T., Kristofikova, Z., Stuchlik, A., and Petrasek, T. (2022). Infectious origin of Alzheimer’s disease: amyloid beta as a component of brain antimicrobial immunity. PLoS Pathog. 18: e1010929, https://doi.org/10.1371/journal.ppat.1010929.Search in Google Scholar PubMed PubMed Central
Walter, S., Jumpertz, T., Hüttenrauch, M., Ogorek, I., Gerber, H., Storck, S.E., Zampar, S., Dimitrov, M., Lehmann, S., Lepka, K., et al.. (2019). The metalloprotease ADAMTS4 generates N-truncated Aβ4–x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer’s disease. Acta Neuropathol. 137: 239–257, https://doi.org/10.1007/s00401-018-1929-5.Search in Google Scholar PubMed
White, M.R., Kandel, R., Tripathi, S., Condon, D., Qi, L., Taubenberger, J., and Hartshorn, K.L. (2014). Alzheimer’s associated β-amyloid protein inhibits influenza A virus and modulates viral interactions with phagocytes. PLoS One 9: e101364, https://doi.org/10.1371/journal.pone.0101364.Search in Google Scholar PubMed PubMed Central
White, M.R., Kandel, R., Hsieh, I.N., De Luna, X., and Hartshorn, K.L. (2018). Critical role of C-terminal residues of the Alzheimer’s associated β-amyloid protein in mediating antiviral activity and modulating viral and bacterial interactions with neutrophils. PLoS One 13: e0194001, https://doi.org/10.1371/journal.pone.0194001.Search in Google Scholar PubMed PubMed Central
Wiatrak, B. and Balon, K. (2021). Protective activity of Aβ on cell cultures (PC12 and THP-1 after differentiation) preincubated with lipopolysaccharide (LPS). Mol. Neurobiol. 8: 1453–1464, https://doi.org/10.1007/s12035-020-02204-w.Search in Google Scholar PubMed PubMed Central
Wirths, O., Walter, S., Kraus, I., Klafki, H.W., Stazi, M., Oberstein, T.J., Ghiso, J., Wiltfang, J., Bayer, T.A., and Weggen, S. (2017). N-truncated Aβ4–x peptides in sporadic Alzheimer’s disease cases and transgenic Alzheimer mouse models. Alzheimers Res. Ther. 9: 80, https://doi.org/10.1186/s13195-017-0309-z.Search in Google Scholar PubMed PubMed Central
Yadollahikhales, G. and Rojas, J.C. (2023). Anti-amyloid immunotherapies for Alzheimer’s disease: a 2023 clinical update. Neurotherapeutics 20: 914–931, https://doi.org/10.1007/s13311-023-01405-0.Search in Google Scholar PubMed PubMed Central
Zampar, S., Klafki, H.W., Sritharen, K., Bayer, T.A., Wiltfang, J., Rostagno, A., Ghiso, J., Miles, L.A., and Wirths, O. (2020). N-terminal heterogeneity of parenchymal and vascular amyloid-β deposits in Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 46: 673–685, https://doi.org/10.1111/nan.12637.Search in Google Scholar PubMed PubMed Central
Zhang, H., Li, X., Wang, X., Xu, J., Elefant, F., and Wang, J. (2023). Cellular response to β-amyloid neurotoxicity in Alzheimer’s disease and implications in new therapeutics. Anim. Models Exp. Med. 6: 3, https://doi.org/10.1002/ame2.12313.Search in Google Scholar PubMed PubMed Central
Zhang, Y., Chen, H., Li, R., Sterling, K., and Song, W.S. (2023). Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future. Transduct. Target Ther. 8: 248, https://doi.org/10.1038/s41392-023-01484-7.Search in Google Scholar PubMed PubMed Central
Zhao, H., Zhu, J., Cui, K., Xu, X., O’Brien, M., Wong, K.K., Kesari, S., Xia, W., and Wong, S.T. (2009). Bioluminescence imaging reveals inhibition of tumor cell proliferation by Alzheimer’s amyloid beta protein. Cancer Cell Int. 9: 15, https://doi.org/10.1186/1475-2867-9-15.Search in Google Scholar PubMed PubMed Central
Zimbone, S., Monaco, I., Gianì, F., Pandini, G., Copani, A.G., Giuffrida, M.L., and Rizzarelli, E. (2018). Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type-1 insulin-like growth factor receptors in neuronal cells. Aging Cell 17: e12684, https://doi.org/10.1111/acel.12684.Search in Google Scholar PubMed PubMed Central
© 2024 Walter de Gruyter GmbH, Berlin/Boston
