Abstract
This review includes a description of the proposed mechanisms to explain the development of Alzheimer’s disease (AD) and strategies for treatment in the light of these mechanisms, with emphasis on the use of polyphenolic compounds as therapeutic agents. The effects of reactive oxygen species ROS and presence of metal redox in the development of AD and treatment strategies with a drug or active substance, based on antioxidant and chelating activity and in its potentiality through signaling pathways are analyzed. Given the importance of polyphenolic compounds as natural antioxidants for treating of AD, in special the flavonoids family, this review takes into account examples of this family, with emphasis on the catechin type flavonoid (-)-epigalocatechin-3-gallate (EGCG). Understanding of how polyphenols are involved at the cellular level (role of its chemical structure in the interaction with the cell and therefore its biological activity is required in order to modulate the interaction and signaling pathways to achieve the desired neurotrophic effects. Effects in vitro often do not correspond to those in vivo. Differences in concentrations and study conditions make that chemical and biological activities of a drug vary. This may be due in part to the need for an adjustment in concentration and time between preclinical and clinical studies. Furthermore, efficient release methods should be investigated, particularly considering that a therapeutic agent for neurological diseases should cross the blood – brain - barrier (BBB). Nano- technology based on controlled release systems of drugs may overcome these limitations. © 2016. Acad. Colomb. Cienc. Ex. Fis. Nat. All rights reserved.References
Alzheimer’s Association. 2016. alz.org/research, Http.www.alz. org/research/science alzheimer_disease_treatments.asp Ansari Niloufar and Fariba Khodagholi. 2013. Natural Products as Promising Drug Candidates for the Treatment of Alzheimer’s Disease: Molecular Mechanism Aspect. Curr. Neuropharmacol., 11 (4): 414-429.
Atwood C.S., Obrenovich M.E., Liu T., Chan H., Perry G., Smith M.A., Martins R.N. 2003 . Amyloid-β: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-β. Brain Res. Brain Res. Rev. 43 (1): 1-16.
Ballard C., Gauthier S., Corbett A., Brayne C., Aarsland D., Jones E. 2011. Alzheimer’s disease. Lancet, 377: 1019-31.
Bentahir M., Nyabi O., Verhamme J., Tolia A., Horre K., Wiltfang J., Esselmann H., de Strooper B. 2006. Presenilin clinical mutations can affect gamma- ecretase activity by different mechanisms. J. Neurochem., 96: 732-742.
Borchardt T., Schmidt C., Camarkis J., Cappai R., Masters C.L., Beyreuther K., Multhaup G. 2000. Differential effects of zinc on amyloid precursor protein (APP) processing in copper-resistant variants of cultured Chinese hamster ovary cells. Cell Mol. Biol. (Noisy-le-Grand, France), 46 (4): 785-95.
Braicu C., Rugina D., Chedea V.S., Tudoran O., Balacescu O., Neagoe I, Socaciu, C. 2010. Protective action of different natural flavan-3-ols against aflatoxin B1-related cytotoxicity. J. Food Biochem., 34: 595-610.
Braicu Cornelia, Pilecki Valentina, Balacescu Ovidiu, Irimie Alexandru & Ioana Berindan Neagoe. 2011. The Relationships Between Biological Activities and Structure of Flavan-3-ols. Int. J. Mol. Sci., 12: 9342-9353.
Cai Z., Yan L.J., Li K., Quazi S.H., Zhao B. Roles of AMPactivated protein kinase in Alzheimer’s disease. (2012). Neuromolecular Med., 14 (1): 1-14.
Carvalho A.N., Firuzi O., Gama M.J., van Horssen J., Saso L. 2016. Oxidative stress and antioxidants in neurological diseases: is there still hope? Drug Des. Devel. Ther., 10: 23-42.
Castellani R. J., Zhu X., Lee H.-G., Smith M. A., & G. Perry. 2009. Molecular pathogenesis of Alzheimer’s disease: reductionist versus expansionist approaches, Int. J. Mol. Sci., 10 (3): 1386-1406.
Cavallucci V., D’Amelio M., Cecconi F. 2012. Aβ toxicity in Alzheimer’s disease. Mol. Neurobiol., 45 (2): 366-78.
Cerutti P. A. (1991). Oxidant stress and carcinogenesis. Eur. J. Clin. Invest., 21 (1): 1-5.
Chasseigneaux S., & B. Allinquant. 2012. Functions of Aβ, sAPPα and sAPPβ: similarities and differences. J. Neurochem., 120 (S1): 99-108.
Cheng Xuan, Lu Zhang, and Ya-Jun Lian. 2015. Molecular Targets in Alzheimer’s disease: From Pathogenesis to Therapeutics. Bio. Med. Research International, Article ID 760758, 6 pages.
Chen Z.P., Schell J.B., Ho C.T., Chen K.Y. 1998. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett., 129 (2): 173-9.
Cherny R.A., Atwood C.S., Xilinas M.E., Gray D.N., Jones W.D., McLean C.A., Barnham K.J., Volitakis I., Fraser F.W., Kim Y., Huang X., Goldstein L.E., Moir R.D., Lim J.T., Beyreuther K., Zheng H., Tanzi R.E., Masters C.L., Bush A.I. 2001. Treatment with a copper-zinc chelator markedly and rapidly inhibits β -amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron, 30: 665-676.
Esteras Noemí, Dinkova-Kostova Albena T. and Abramov Andrey Y. 2016. Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function. Biol. Chem., 397 (5): 383-400.
Finder, V. H. and R Glockshuber. 2007. Amyloid-beta aggregation. Neurodegenerative Diseases, 4: 13-27.
Finder, V. H. 2010. Alzheimer’s disease a general introduction and pathomechanism. J. Alzheimers Dis., 22 (3): 5-19.
Fridovich.I. 1978. The biology of oxygen radicals. Science, 201 (4359): 875-80.
Fridovich. I. 1999. Fundamental aspects of reactive oxygen species, or what’s the matter with oxygen. Ann. N Y. Acad. Sci., 893: 3-18.
Geerts H, Grossberg G.T. 2006. Pharmacology of acetylcholinesterase inhibitors and N-methyl- -aspartate receptors for combination therapy in the treatment of Alzheimer’s disease. J. Clin. Pharmacol., 46 (7 S1): 8S-16S.
Gilgun-Sherki Y., Melamed E., Offen D. 2001. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology,40: 959-975.
Godoy Juan A., Juvenal A. Rios, Juan M. Zolezzi, Nady Braidy & Nibaldo C. Inestrosa. 2014. Signaling pathway cross talk in Alzheimer’s disease. Cell Communication and Signaling, 12: 23.
González-Manzano Susana, Ana M. González-Paramás, Laura Delgado, Simone Patianna, Felipe Surco-Laos, Montserrat Dueñas, & Celestino Santos-Buelga. 2012. Oxidative Status of Stressed Caenorhabditis elegans Treated with Epicatechin. J. Agric. Food Chem., 60 (36): 8911-8916.
Gough Mallory, Parr-Sturgess Catherine, & Edward Parkin. 2011. Review Article Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer’s disease. Biochemistry Research International, Article ID 721463, 13 pages.
Hardy J.A., Higgins G.A. 1992. Alzheimer’s disease: the amyloid cascade hypothesis. Science, 256: 184-185.
Hegde Muralidhar L., P. Bharathi, Anitha Suram, Chitra Venugopal, Ramya Jagannathan, Pankaj Poddar, Pullabhatla Srinivas, Kumar Sambamurti, Kosagisharaf Jagannath Rao, Janez Scancar, Luigi Messori, Luigi Zecca, & Paolo Zatta. 2009. Challenges Associated with Metal Chelation Therapy in Alzheimer’s Disease. J. Alzheimers Dis., 17 (3): 457-468
Hooper C., Killick R., Lovestone S. 2008. The GSK3 hypothesis of Alzheimer’s disease. J. Neurochem. 104 (6): 1433-9.
Inestrosa Nibaldo C., & Varela-Nallar Lorena. 2014. Wnt signaling in the nervous system and in Alzheimer’s disease. Journal of Molecular Cell Biology. 6: 64-74.
Iqbal Khalid, Fei Liu, Cheng-Xin Gong, & Inge Grundke- qbal. 2010. Tau in Alzheimer Disease and Related Tauopathies. Curr. Alzheimer Res. 8: 656-664.
Iwatsubo, T. 1998. Abeta42, presenilins, and Alzheimer’s disease. Neurobiology of Aging. 19: S11-3.
Jankowsky J.L., Fadale D.J., Anderson J., Xu G.M., Gonzales V., Jenkins N.A., Copeland N.G., Lee M.K., Younkin L.H., Wagner S.L.,Younkin S.G., Borchelt D.R. 2004. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo. Evidence for augmentation of a 42-specific gamma secretase. Human Molecular Genetics. 13: 159-70.
Jarrett J.T., Berger E. P. & P. T. Lansbury, Jr. 1993. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer’s disease. Biochemistry. 32: 4693-7.
Joshi Gururaj & Jeffrey A. Johnson. 2012. The Nrf2-ARE pathway: a valuable therapeutic target for the treatment of neurodegenerative diseases. Recent Pat CNS Drug Discov., 7 (3): 218-229.
Karunaweera Niloo, Raju Ritesh, Gyengesi Erika & Münch Gerald. 2015. Plant polyphenols as inhibitors of NF-kB induced cytokine production- a potential anti-inflammator treatment for Alzheimer’s disease. Frontiers in Molecular Neuroscience, 8: 24.
Khodagholi Fariba, Eftekharzadeh Bahareh, Maghsoudi, Rezaei Nader Parisa Fathi. 2010. Chitosan prevents oxidative stress-induced amyloid β formation and cytotoxicity in NT2 neurons: involvement of ranscription factors Nrf2 and NF-Κb. Molecular and Cellular Biochemistry. 337 (1): 39-51.
Kim Eun Kyung, Choi Eui-Ju. 2010. Pathological roles of MAPK signaling pathways in human diseases. Biochimica et Biophysica Acta. 1802: 396-405.
Kim Hae-Suk, Quon Michael J., Kim Jeong-a. 2014. New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biology. 2: 187-195.
Kim Taehyun, Hinton David J., & Choi Doo-Sup. 2011. Protein Kinase C-Regulated Aβ Production and Clearance. International Journal of Alzheimer’s disease, (2011), Article ID 857368, 7 pages.
Koh S.H., Kim S.H., Kwon H., Kim J.G., Kim J.H., Yang K.H., Kim J., Kim S.U., Yu H.J., Do B.R., Kim K.S., Jung H.K. 2004. Phosphatidylinositol-3 kinase/Akt and GSK-3 mediated cytoprotective effect of epigallocatechin gallate on oxidative stress-injured neuronal-differentiated N18D3 cells. Neurotoxicology. 25 (5): 793-802.
Kondo K., Kurihara M., Miyata N., Suzuki T., Toyoda M. 1999. Scavenging mechanisms of (−)-epigallocatechin gallate and (−)-epicatechin gallate on peroxyl radicals and formation of superoxide during the inhibitory action. Free Radic. Biol. Med. 27 (7-8): 855-863.
Kotebagilu Namratha Pai, Vanitha Reddy Palvai & Asna Urooj. 2015. Ex Vivo Antioxidant Activity of Selected. Medicinal Plants against Fenton Reaction-Mediated Oxidation of Biological Lipid Substrates, Article ID 728621, 7 pages.
Kou Xianjuan, Kirberger Michael, Yang Yi, Chen Ning. 2013. Natural products for cancer prevention associated with Nrf2–ARE pathway. Food Science and Human Wellness, 2 (1): 22-28.
Krauss, Gerhard. 2008. Biochemistry of Signal Transduction and Regulation. Wiley-VCH, p. 15. ISBN 978-3527313976 Kroemer G. and Reed J.C. 2000. Mitochondrial control of cell death. Nat. Med. 6 (5):513-519.
Lee J.W., Lee Y.K., Ban J.O., Ha T.Y., Yun Y.P., Han S.B., Oh K.W., Hong J.T. 2009. Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J. Nutr. 139 (10):1987-93.
Lee V.M., Goedert M., Trojanowski J.Q. 2001. Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24: 1121-1159.
Leopoldini M., Russo N., Toscano M. 2011. The olecular basis of working mechanism of natural polyphenolic antioxidants. Food Chem. 125: 288-306.
Lin Chih-Li , Chen Ta-Fu, Chiu Ming-Jang, Way Tzong-Der, Lin Jen-Kun. 2009. Epigallocatechin gallate (EGCG) suppresses amyloid-induced neurotoxicity through inhibiting c-Abl/FE65 nuclear translocation and GSK3 activation. Neurobiology of Aging. 30: 81-92.
Mandel S., Amit T., Bar-Am O., Youdim M.B. 2007. Iron dysregulation in Alzheimer’s dis ease: multimodal brain permeable iron chelating drugs, possessing neuroprotectiveneurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents. Prog. Neurobiol., 82: 348-360.
Mansuri M.L.,Parihar P.,Solanki I., Parihar M.S. (2014). Flavonoids in modulation of cell survival signalling pathways. Genes Nutr. 9 (3): 400.
Mattson M.P. and M.K. Meffert. 2006. Roles for NF-kB in nerve cell survival, plasticity, and disease. Cell Death and Differentiation. 13: 852-860.
Menard C., Bastianetto S., Quirion R. 2013. Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma. Frontiers in Cellular Neuroscience. 7: 281-8.
Misra Parimal, Owuor Edward D., Li Wenge, Yu Songtao, Qi Chao, Meyer Kirstin, Zhu Yi-Jun, Rao M. Sambasiva, Tony Kong A.-N. & Reddy Janardan K. 2002. Phosphorylation of transcriptional coactivator peroxisome proliferatoractivated receptor (PPAR)-inding protein (PBP), Stimulation of transcriptional regulation by mitogenactivated protein kinase. Journal of Biological Chemistry. 277 (50): 48745-48754.
Monsalve Y., Tosi G., Ruozi B., Belletti D., Vilella A., Zoli M., Vandelli M.A., Forni F., López B.L., Sierra L. 2015. PEG-g-chitosan nanoparticles functionalized with the monoclonal antibody OX26 for brain drug targeting. Nanomedicine. (10, 11): 1735-50.
Moskovitz J., Yim K.A., Choke P.B. 2002. Free radicals and disease. Arch Biochem Biopsy’s. 397: 354-359.
Munin Aude and Florence Edwards-Lévy. 2011. Encapsulation of Natural Polyphenolic Compounds; a Review. Pharmaceutics. (3, 4): 793-829.
Na H.K., Surh Y.J. 2006. Transcriptional regulation via cysteine thiol modification: a novel molecular strategy for chemoprevention and cytoprotection. Mol. Carcinog. (45, 6): 368-80.
Nicolas M. and B. A. Hassan. 2014. Amyloid precursor protein and neural development. Development. 141 (13): 2543-2548.
Nilsberth C., Westlind-Danielsson A., Eckman C.B., Condron M.M., Axelman K., Forsell C., Stenh C., Luthman J., Teplow D.B., Younkin S.G. 2001. The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat. Neurosci. 4: 887-893.
Oddo S., Caccamo A., Cheng D., Jouleh B., Torp R., LaFerla F.M. 2007. Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic mice. J. Neurochem. 102: 1053-1063.
Opazo C., Huang X., Cherny R. 2002. Metalloenzyme- ike activityof Alzheimer’s disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2. J. Biol. Chem. 277: 40302-40308.
Ou Jiang-Rong, Meng-Shan Tan, An-Mu Xie, Jin-Tai Yu, & Lan Tan. 2014. Heat Shock Protein 90 in Alzheimer’s Disease. Bio Med Research International Article ID 796869, 7 pages.
Pasello Michela, Michelacci Francesca, Isabella Scionti, Hattinger Claudia Maria, Zuntini Monia, Caccuri Anna Maria, Scotlandi Katia, Picci Piero, & Serra Massimo. 2008. Overcoming Glutathione S-Transferase P1–Related Cisplatin Resistance in Osteosarcoma. Cancer Res. 68: 16.
Piao C. S., Kim D.-S., Ha K.-C., Kim H.-R., Chae H.-J., and Chae S.-W. 2011. The protective effect of epigallocatechin-3 gallate on ischemia/reperfusion injury in isolated rat hearts:an ex vivo approach. Korean Journal of Physiology and Pharmacology. 15 (5): 259-266.
Popa-Wagner Aurel, Smaranda Mitran, Senthilkumar Sivanesan, Edwin Chang & Ana-Maria Buga. 2013. ROS and Brain Diseases: The Good, the Bad, and the Ugly. Oxidative Medicine and Cellular Longevity, Article ID 963520, 14 pages.
Kevin Punsky. 2014. Pathway that contributes to Alzheimer’s disease revealed by research. Science News, https://www.sciencedaily.com/releases/2014/09140919140738.htm.
Rao K.S.J., Rao R.V., Shanmugavelu P., Menon R.B. 1999. Trace elements in Alzheimer’s disease brain: A new hypothesis. Alzheimers reports. 2: 241-246.
Romeo L., Intrieri M., D’Agata V., Mangano N.G., Oriani G., Ontario M.L., Scapagnini G. 2009. The major green tea polyphenol, (-)-epigallocatechin-3-gallate, induces heme oxygenase in rat neurons and acts as an effective neuroprotective agent against oxidative stress. J. Am. Coll. Nutr., (492S-499S).
Rossor M. N. 1993. Molecular pathology of Alzheimer’s disease. Journal of Neurology, Neurosurgery & Psychiatry. 56: 583-586.
Rui-Chun Lu, Meng-Shan Tan, Hao Wang, An-Mu Xie, Jin-Tai Yu, & Lan Tan. 2014. Heat Shock Protein 70 in Alzheimer’s disease. Bio Med. Research International, Article ID 435203, 8 pages.
Scheuner D., Eckman C., Jensen M., Song X., Citron M., Suzuki N., Bird T.D., Hardy J., Hutton M., Kukull W., Larson E., Levy-Lahad E., Viitanen M., Peskind E., Poorkaj P., Schellenberg G., Tanzi R., Wasco W., Lannfelt L., Selkoe D., Younkin S. 1996. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat. Med. (2, 8): 864-70.
Schipper H.M. 2004. Redox neurology Visions of an emerging subspecialty. Ann. N.Y. Acad. Sci. 1012: 342-355.
Singh Neha Atulkumar, Mandal Abul Kalam Azad & Kha Zaved Ahmed. 2016. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutrition Journal 15: 60.
Sonee M., Sum T., Wang C., Mukherjee S.K. 2004. The soy isoflavone, genistein, protects human cortical neuronal cells from oxidative stress. Neurotoxicology. 25: 885-91.
Spencer Jeremy P.E. 2007. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr. (2, 3): 257-273.
Spillantini M.G., Murrell J.R., Goedert M., Farlow M.R., Klug A., Ghetti B. 1998. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl. Acad. Sci. USA. (95, 13): 7737-7741
Suzuki N., Cheung T., Cai X.D., Odaka A., Otvos L. Jr., Eckman C., Golde T.E., Younkin S.G. 1994. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science. (264, 5163): 1336-40.
Suzuki Y.J., Forman H.J., Sevanian A. 1997. Oxidant as stimulators of signal transduction. Free Radic. Biol. Med., 22: 269-285.
Swaran J.S. 2009. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med. Cell. Longev. (2, 4): 191-206.
Takashima Akihiko, Noguchi Kaori, Michel Gilles, Mercken Marc, Hoshi Minako, Ishiguro Koichi, Imahori Kazutomo. 1996. Exposure of rat hippocampal neurons to amyloid β peptide (25-35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I/glycogen synthase kinase-3β. Neuroscience Letters. (203, 1): 33-36.
Tarapore Rohinton S., Siddiqui Imtiaz A., & Mukhtar Hasan. 2012. Modulation of Wnt/β-catenin signaling pathway by bioactive food components. Carcinogenesis. 33 (3): 483-491.
Treiber C., Simons A., Strauss M., Hafner M., Cappai R., Bayer T.A., Multhaup G. 2004. Clioquinol mediates copper uptake and counteracts copper efflux activities of the amyloid precursor protein of Alzheimer’s disease. J. Biol. Chem. 279: 51958-51964.
Turner, P. R., O’Connor, K., Tate, W. P., & Abraham, W. C. 2003. Roles of amyloid protein and its fragments in regulating neural activity, plasticity and memory. Prog. Neurobiol. 70: 1-32.
Uttara Bayani, Ajay V. Singh, Paolo Zamboni, & R.T Mahajan. 2009. Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr. Neuropharmacol. (7, 1): 65-74.
Vassar R., Bennett B.D., Babu-Khan S., Kahn S., Mendiaz E.A., Denis P., Teplow D.B., Ross S., Amarante P., Loeloff R., Luo Y., Fisher S., Fuller J., Edenson S., Lile J., Jarosinski M.A., Biere A.L., Curran E., Burgess T., Louis J.C, Collins F., Treanor J., Rogers G., Citron M. 1999. Betasecretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science, (286, 5440): 735-41.
Velayutham P., Babu A., Liu D. 2008. Green tea catechins and cardiovascular health: An update. Curr. Med. Chem. 15: 1840-1850
Wang C., Yu J.T., Miao D., Wu Z.C., Tan M.S., Tan L. (2014). Targeting the mTOR signaling network for Alzheimer’s disease therapy. Mol. Neurobiol. 120-35.
Wan Wenbin, Xia Shijin, Kalionis Bill, Liu Lumei, & Li Yaming. 2014. The Role of Wnt Signaling in the Development of Alzheimer’s Disease: A Potential Therapeutic Target? Bio. Med. Research International, Article ID 301575, 9 pages.
Watt T.Nicole, Whitehouse Isobel J. and Nigel M. Hooper. 2011. Review Article. The Role of Zinc in Alzheimer’s disease. Inter. J Alzheimers Dis., Article ID 971021, 10 pages.
Wu C. C., Hsu M. C., Hsieh C. W., Lin J. B., Lai P. H., Wung B. S. 2006. Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sciences. (78, 25):2889-2897.
Younkin, S. G. 1998. The role of A beta 42 in Alzheimer’s disease. Journal of Physiology. 92 (3-4): 289-92.
Zhang H., Ma Q., Zhang,Y.-W., & H. Xu. 2012. Proteolytic processing of Alzheimer’s β-amyloid precursor protein. Journal of Neurochemistry. 120 (1): 9-21.
Zhao Yan & Baolu Zha. 2013. Oxidative Stress and the Pathogenesis of Alzheimer’s disease. Oxidative Medicine and Cellular Longevity, Article ID 316523, 10 pages Zheng H. & E. H. Koo. 2006. The amyloid precursor protein: beyond amyloid, Molecular Neurodegeneration. 1:5.
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