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Enzimas degradadoras de amiloide en la Enfermedad de Alzheimer: de las moléculas a la terapia genética
Resumen
La enfermedad de Alzheimer (EA) es la principal forma de demencia en adultos mayores a nivel mundial. En el año 2010 se estimó que 35.6 millones de personas padecen esta enfermedad y se proyectó que esta cifra se triplicará para el año 2050. De acuerdo con la hipótesis amiloide, la producción y agregación del péptido beta amiloide (A-beta) es el agente inicial en el desarrollo de la EA. El péptido A-beta se genera a partir del procesamiento proteolítico de la proteína precursora de amiloide (APP), y su degradación depende de un grupo de proteínas colectivamente conocidas como enzimas degradadoras de amiloide (EDA), las cuales se reducen durante el envejecimiento y particularmente en la EA. La terapia genética consiste en la restauración de la expresión genética de una proteína deficiente para tratar una enfermedad. La restauración o sobreexpresión cerebral de las EDA reduce los niveles y agregados de A-beta, y mejora el aprendizaje y la memoria en modelos animales de la EA. En la presente revisión se describe el papel de las EDA en la regulación de los niveles de A-beta, así como su uso potencial en la terapia genética contra la EA.
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Referencias
Goedert M, Spillantini MG. A century of Alzheimer's disease. Science. 2006;314(5800):777-81.
Wortmann M. Dementia: a global health priority - highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 2012;4(5):40.
Gutierrez-Robledo LM, Arrieta-Cruz I. Dementia in Mexico: The need for a National Alzheimer's Plan. Gac Med Mex. 2015;151(5):667-73.
Balin BJ, Hudson AP. Etiology and pathogenesis of late-onset Alzheimer's disease. Curr Allergy Asthma Rep. 2014;14(3):417.
Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging. 2004;25(5):641-50.
Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci. 2015;9:124.
Chintamaneni M, Bhaskar M. Biomarkers in Alzheimer's disease: a review. ISRN Pharmacol. 2012;2012:984786.
Ba M, Kong M, Li X, Pin-Ng K, Rosa-Neto P, Gauthier S. Is ApoE varepsilon 4 a good biomarker for amyloid pathology in late onset Alzheimer's disease?
Transl Neurodegener. 2016;5:20.
Kumar S, Reddy PH. Are circulating microRNAs peripheral biomarkers for Alzheimer's disease? Biochim Biophys Acta. 2016;1862(9):1617-27.
Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer's disease. Ther Adv Neurol Disord. 2013;6(1):19-33.
Wisniewski T, Drummond E. Developing therapeutic vaccines against Alzheimer's disease. Expert Rev Vaccines. 2016;15(3):401-15.
Alves S, Fol R, Cartier N. Gene Therapy Strategies for Alzheimer's Disease: An Overview. Hum Gene Ther. 2016;27(2):100-7.
Hippius H, Neundorfer G. The discovery of Alzheimer's disease. Dialogues Clin Neurosci. 2003;5(1):101-8.
Pritchard SM, Dolan PJ, Vitkus A, Johnson GV. The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics.
J Cell Mol Med. 2011;15(8):1621-35.
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608.
Schellenberg GD, Montine TJ. The genetics and neuropathology of Alzheimer's disease. Acta Neuropathol. 2012;124(3):305-23.
Drummond E, Wisniewski T. Alzheimer's disease: experimental models and reality. Acta Neuropathol. 2017;133(2):155-175.
Zhang X, Song W. The role of APP and BACE1 trafficking in APP processing and amyloid-beta generation. Alzheimers Res Ther. 2013;5(5):46.
Baranello RJ, Bharani KL, Pamaraju V, Chopra N, Lahiri DK, Greig NH, et al. Amyloid-beta protein clearance and degradation (ABCD) pathways and their role in Alzheimer's disease. Curr Alzheimer Res. 2015;12(1):32-46.
NalivaevaNN, Belyaev ND, Kerridge C, Turner AJ. Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer's disease. Front Aging Neurosci. 2014;6:235.
Turner AJ, Isaac RE, Coates D. The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Bioessays. 2001;23(3):261-9.
Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE. Structural analysis of neprilysin with various specific and potent inhibitors.
Acta Crystallogr D Biol Crystallogr. 2004;60(Pt 2):392-6.
Carson JA, Turner AJ. Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases? J Neurochem. 2002;81(1):1-8.
Mouri A, Zou LB, Iwata N, Saido TC, Wang D, Wang MW, et al. Inhibition of neprilysin by thiorphan (i.c.v.) causes an accumulation of amyloid beta and impairment of learning and memory. Behav Brain Res. 2006;168(1):83-91.
Oh JH, Choi S, Shin J, Park JS. Protective effect of recombinant soluble neprilysin against beta-amyloid induced neurotoxicity. Biochem Biophys Res Commun. 2016;477(4):614-9.
Mizuta N, Yanagida K, Kodama T, Tomonaga T, Takami M, Oyama H, et al. Identification of Small Peptides in Human Cerebrospinal Fluid upon Amyloid-beta Degradation. Neurodegener Dis. 2017;17(2-3):103-109.
Yamamoto N, Fuji Y, Kasahara R, TanidaM, Ohora K, Ono Y, et al. Simvastatin and atorvastatin facilitates amyloid beta-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways. Glia. 2016;64(6):952-62.
Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, et al. Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo. J Neurosci Res. 2006;84(8):1871-8.
Huttenrauch M, Baches S, Gerth J, Bayer TA, Weggen S, Wirths O. Neprilysin deficiency alters the neuropathological and behavioral phenotype in the 5XFAD mouse model of Alzheimer's disease. J Alzheimers Dis. 2015;44(4):1291-302.
Nilsson P, Loganathan K, Sekiguchi M, Winblad B, Iwata N, Saido TC, et al. Loss of neprilysin alters protein expression in the brain of Alzheimer's disease model mice. Proteomics. 2015;15(19):3349-55.
Poirier R, Wolfer DP, Welzl H, Tracy J, Galsworthy MJ, Nitsch RM, et al. Neuronal neprilysin overexpression is associated with attenuation of Abeta-related spatial memory deficit. Neurobiol Dis. 2006;24(3):475-83.
Devi L, Ohno M. A combination Alzheimer's therapy targeting BACE1 and neprilysin in 5XFAD transgenic mice. Mol Brain. 2015;8:19.
Yasojima K, Akiyama H, McGeer EG, McGeer PL. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide. Neurosci Lett. 2001;297(2):97-100.
Wang DS, Lipton RB, Katz MJ, Davies P, Buschke H, Kuslansky G, et al. Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological aging. J Neuropathol Exp Neurol. 2005;64(5):378-85.
Zhuravin IA, Nalivaeva NN, Kozlova DI, Kochkina EG, Fedorova YB, Gavrilova SI. [The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer's disease]. Zh Nevrol Psikhiatr Im S S Korsakova, 2015;115(12):110-7.
Morales-Corraliza J, Wong H, Mazzella MJ, Che S, Petkova E, et al. Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-beta Alterations in a Monkey Model of Type 1 Diabetes. J Neurosci. 2016;36(15):4248-58.
Russo R, Borghi R, Markesbery W, Tabaton M, Piccini A. Neprylisin decreases uniformly in Alzheimer's disease and in normal aging. FEBS Lett. 2005;579(27):6027-30.
Duckworth WC, Bennett RG, Hamel FG. Insulin degradation: progress and potential. Endocr Rev. 1998;19(5):608-24.
Hersh LB. The insulysin (insulin degrading enzyme) enigma. Cell Mol Life Sci. 2006;63(21):2432-4.
Pérez A, Morelli L, Cresto JC, Castaño EM. Degradation of soluble amyloid beta-peptides 1-40, 1-42, and the Dutch variant 1-40Q by insulin degrading enzyme from Alzheimer disease and control brains. Neurochem Res. 2000;25(2):247-55.
Hubin E, Cioffi F, Rozenski J, van Nuland NA, Broersen K. Characterization of insulin-degrading enzyme-mediated cleavage of Abeta in distinct aggregation states. Biochim Biophys Acta. 2016;1860(6):1281-90.
Moore KM, Girens RE, Larson SK, Jones MR, Restivo JL, Holtzman DM, et al. A spectrum of exercise training reduces soluble A-beta in a dose-dependent manner in a mouse model of Alzheimer's disease. Neurobiol Dis. 2016;85:218-24.
Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, et al. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A. 2003;100(7):4162-7.
Farris W, Mansourian S, Leissring MA, Eckman EA, Bertram L, Eckman CB, et al. Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. Am J Pathol. 2004;164(4):1425-34.
Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, Sun X, et al. Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron. 2003;40(6):1087-93.
Haque R, Nazir A. Identification and functional characterization of a putative IDE, C28F5.4 (ceIDE-1), in Caenorhabditis elegans: Implications for Alzheimer's disease. Biochim Biophys Acta. 2016;1860(11 Pt A):2454-62.
Bernstein HG, Ansorge S, Riederer P, Reiser M, Frölich L, Bogerts B. Insulin-degrading enzyme in the Alzheimer's disease brain: prominent localization in neurons and senile plaques. Neurosci Lett. 1999;263(2-3):161-4.
Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, Roth RA, et al. Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele. Am J Pathol. 2003;162(1):313-9.
Gutierrez-Hermosillo H, Díaz de León-González E, Palacios-Corona R, Cedillo-Rodríguez JA, Camacho-Luis A, Reyes-Romero MA, et al. C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study. Med Clin (Barc). 2015;144(4):151-5.
Wang S, He F, Wang Y. Association between polymorphisms of the insulin-degrading enzyme gene and late-onset Alzheimer disease.
J Geriatr Psychiatry Neurol. 2015;28(2):94-8.
Johnson GD, Stevenson T, Ahn K. Hydrolysis of peptide hormones by endothelin-converting enzyme-1. A comparison with neprilysin.
J Biol Chem. 1999;274(7):4053-8.
Eckman EA, Reed DK, Eckman CB. Degradation of the Alzheimer's amyloid beta peptide by endothelin-converting enzyme.
J Biol Chem. 2001;276(27):24540-8.
Pacheco-Quinto J, Eckman EA. Endothelin-converting enzymes degrade intracellular beta-amyloid produced within the endosomal/lysosomal pathway and autophagosomes. J Biol Chem. 2013;288(8):5606-15.
Eckman EA, Watson M, Marlow L, Sambamurti K, Eckman CB. Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J Biol Chem. 2003;278(4):2081-4.
Naidoo V, Naidoo S, Mahabeer R, Raidoo DM. Cellular distribution of the endothelin system in the human brain. J Chem Neuroanat. 2004;27(2):87-98.
Pacheco-Quinto J, Eckman CB, Eckman EA. Major amyloid-beta-degrading enzymes, endothelin-converting enzyme-2 and neprilysin, are expressed by distinct populations of GABAergic interneurons in hippocampus and neocortex. Neurobiol Aging. 2016;48:83-92.
Weeraratna AT, Kalehua A, Deleon I, Bertak D, Maher G, Wade MS, et al. Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues. Exp Cell Res. 2007;313(3):450-61.
Wang S, Wang R, Chen L, Bennett DA, Dickson DW, Wang DS. Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer's brain. J Neurochem. 2010;115(1):47-57.
Palmer JC, Shabnam B, Kehoe PG, Love S. Endothelin-converting enzyme-2 is increased in Alzheimer's disease and up-regulated by A-beta. Am J Pathol. 2009;175(1):262-70.
Palmer JC, Tayler HM, Love S. Endothelin-converting enzyme-1 activity, endothelin-1 production, and free radical-dependent vasoconstriction in Alzheimer's disease. J Alzheimers Dis. 2013;36(3):577-87.
Hassanin OM, Moustafa M, El Masry TM. Association of insertion–deletion polymorphism of ACE gene and Alzheimer’s disease in Egyptian patients. Egyptian Journal of Medical Human Genetics. 2014;15(4):355-360.
Rygiel K. Can angiotensin-converting enzyme inhibitors impact cognitive decline in early stages of Alzheimer's disease? An overview of research evidence in the elderly patient population. J Postgrad Med. 2016;62(4):242-248.
Kresina TF, Branch AD. Molecular Medicine and Gene Therapy: an introduction, in Molecular Medicine and Gene TherapyT.F. Kresina, Editor. 2002; Wiley-Liss, Inc.: 1-24.
Li Y, Wang J, Zhang S, Liu Z. Neprilysin gene transfer: A promising therapeutic approach for Alzheimer's disease. J Neurosci Res. 2015;93(9):1325-9.
Marr RA, Rockenstein E, Mukherjee A, Kindy MS, Hersh LB, Gage FH, et al. Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. J Neurosci. 2003;23(6):1992-6.
Spencer B, Marr RA, Rockenstein E, Crews L, Adame A, Potkar R, et al. Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice. BMC Neurosci. 2008;9:109.
Iwata N, Mizukami H, Shirotani K, Takaki Y, Muramatsu S, Lu B, et al. Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain. J Neurosci. 2004;24(4):991-8.
Hong CS, Goins WF, Goss JR, Burton EA, Glorioso JC. Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer's disease-related amyloid-beta peptide in vivo. Gene Ther. 2006;13(14):1068-79.
Hemming ML, Patterson M, Reske-Nielsen C, Lin L, Isacson O, Selkoe DJ. Reducing amyloid plaque burden via ex vivo gene delivery of an A-beta-degrading protease: a novel therapeutic approach to Alzheimer disease. PLoS Med. 2007;4(8):e262.
Blurton-Jones M, Spencer B, Michael S, Castello NA, Agazaryan AA, Davis JL, et al. Neural stem cells genetically-modified to express neprilysin reduce pathology in Alzheimer transgenic models. Stem Cell Res Ther. 2014;5(2):46.
Takamatsu K, Ikeda T, Haruta M, Matsumura K, Ogi Y, Nakagata N, et al. Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2. Stem Cell Research. 2014;13(3, Part A):442-453.
Guan H, Liu Y, Daily A, Police S, Kim MH, Oddo S, et al. Peripherally expressed neprilysin reduces brain amyloid burden: a novel approach for treating Alzheimer's disease. J Neurosci Res. 2009;87(6):1462-73.
Lebson L, Nash K, Kamath S, Herber D, Carty N, Lee D, et al. Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice. J Neurosci. 2010;30(29):9651-8.
Iwata N, Sekiguchi M, Hattori Y, Takahashi A, Asai M, Ji B, et al. Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice. Sci Rep. 2013;3:1472.
Liu Y, Studzinski C, Beckett T, Guan H, Hersh MA, Murphy MP, et al. Expression of neprilysin in skeletal muscle reduces amyloid burden in a transgenic mouse model of Alzheimer disease. Mol Ther. 2009;17(8):1381-6.
Park MH, Lee JK, Choi S, Ahn J, Jin HK, Park JS, et al. Recombinant soluble neprilysin reduces amyloid-beta accumulation and improves memory impairment in Alzheimer's disease mice. Brain Res. 2013;1529:113-24.
Barua UN, Miners JS, Bienemann AS, Wyatt MJ, Welser K, Tabor AB, et al. Convection-enhanced delivery of neprilysin: a novel amyloid-beta-degrading therapeutic strategy. J Alzheimers Dis. 2012;32(1):43-56.
Li Y, Wang J, Liu J, Liu F. A novel system for in vivo neprilysin gene delivery using a syringe electrode. J Neurosci Methods, 2010;193(2):226-31.
Li Y, Wang J, Grebori C, Foote M, Liu F. A syringe-focused ultrasound device for simultaneous injection of DNA and gene transfer.
J Gene Med. 2012;14(1):54-61.
Lin CY, Perche F, Ikegami M, Uchida S, Kataoka K, Itaka K. Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles. J Control Release. 2016;235:268-75.
Pivovarova O, Höhn A, Grune T, Pfeiffer AF, Rudovich N. Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer's disease?
Ann Med. 2016;48(8):614-624.
Carty N, Nash KR, Brownlow M, Cruite D, Wilcock D, Selenica MLB, et al. Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice. PLoS One. 2013;8(3):e59626.
Fol R, Braudeau J, Ludewig S, Abel T, Weyer SW, Roederer JP, et al. Viral gene transfer of APPsalpha rescues synaptic failure in an Alzheimer's disease mouse model. Acta Neuropathol. 2016;131(2):247-66.
Pacheco-Quinto J, Herdt A, Eckman CB, Eckman EA. Endothelin-converting enzymes and related metalloproteases in Alzheimer's disease. J Alzheimers Dis. 2013;33(Suppl 1):S101-10.
Carty N, Nash K, Lee D, Mercer M, Gottschall PE, Meyers C, et al. Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Abeta deposits in APP + PS1 transgenic mice. Mol Ther. 2008;16(9):1580-6.
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