Role of Neprilysin in Synaptic Plasticity and Memory
PDF (English)

Ключевые слова

Старение
Болезнь Альцгеймера
С-концевой фрагмент
елка предшественника амилоидного пептида
Амилоидный пептид
Амилоид-деградирующий фермент
Когнитивный дефицит
Кора мозга
Дендритные шипики
Развитие
Эндопептидаза-24.11
Эпигенетическая регуляция
Деацетилазы гистонов
Гиппокамп
Память
Пренатальная гипоксия
Стриатум

Как цитировать

Наливаева, Н. Н., Васильев, Д. С., Дубровская, Н. М., Turner, A. J., & Журавин, И. А. (2020). Role of Neprilysin in Synaptic Plasticity and Memory. Российский физиологический журнал им. И. М. Сеченова, 106(10), 1191–1208. https://doi.org/10.31857/S0869813920100076

Аннотация

Неприлизин (НЕП, нейтральная эндопептидаза, эндопептидаза-24.11) является важным ферментом, наиболее представленным в почках и печени и расщепляющим большое число биологически важных пептидов.  Он играет важную роль в регуляции кровяного давления и нормального функционирования практически всех органов и тканей, а его дисрегуляция приводит к развитию таких заболеваний, как сердечная недостаточность, рак, диабет и хроническое воспаление. Он также является важной нейропептидазой, прекращая действие таких нейропептидов как энкефалины, субстанция Р, соматостатин, которые принимают участие в сигнальных и регуляторных прцессах в мозге. НЕП является также основным амилоид-деградирующим ферментом, что делает его важной терапевтической мишенью в области болезни Альцгеймера (БА).  Наши исследования показали, что экспрессия НЕП снижается с возрастом в структурах мозга, принимающих участие в формировании памяти и наиболее повреждаемых при БА. Более того, экспрессия НЕП снижается при гипоксических воздействиях, а пренатальная гипоксия у крыс приводит к его дефициту в ряде структур мозга как в процессе развития, так и во взрослом мозге, что коррелирует со сниженным числом лабильных дендритных шипиков и когнтивным дефицитом. Используя модель пренатальной гипоксии у крыс, мы провели анализ эффективности ряда соединений (ингибиторов каспаз, деацетилаз  гистонов, тирозинкиназ, агонистов ядерных ретиноидных Х рецепторов, а также антиоксиданта эпигаллокатехин галлата), которые посредством разных механизмов способны восстанавливать экспрессию НЕП, сниженную в результате пренатальной гипоксии,  и улучшать когнитивные функции животных. В этой статье мы приводим анализ литературных и наших данных о роли НЕП в синаптической пластичности, нейрональной аткивности и когнитивных функциях и очерчиваем ряд современных подходов для регуляции его экспрессии и активности в ткани мозга.     

https://doi.org/10.31857/S0869813920100076
PDF (English)

Литература

Fulcher I.S., Kenny A.J. Proteins of the kidney microvillar membrane. The amphipathic forms of endopeptidase purified from pig kidneys. Biochem J. 211:743–753. 1983. https://doi.org/ 10.1042/bj2110743.

Spillantini M.G., Sicuteri F., Salmon S., Malfroy B. Characterization of endopeptidase 3.4.24.11 ("enkephalinase") activity in human plasma and cerebrospinal fluid. Biochem Pharmacol. 39:1353-1356. 1990.

Kuruppu S., Rajapakse N.W., Minond D., Smith A.I. Production of soluble Neprilysin by endothelial cells. Biochem Biophys Res Commun. 446(2):423-427. 2014.

Kerr M.A., Kenny A.J. The purification and specificity of a neutral endopeptidase from rabbit kidney brush border. Biochem J. 137:477–488. 1974.

Nalivaeva N.N., Turner A.J. Neprilysin. In: Neil D. Rawlings and Guy S. Salvesen, editors, Handbook of Proteolytic Enzymes. Oxford: Academic Press. pp. 612-619. 2013.

Matsas R., Kenny A.J., Turner A.J. An immunohistochemical study of endopeptidase-24.11 ("enkephalinase") in the pig nervous system. Neuroscience. 18: 991-1012. 1986.

Letarte M., Vera S., Tran R., Addis J.B.L., Onizuka R.J., Quackenbush E.J., Jongeneel C.V., McInnes R.R. Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med. 168: 1247–1253. 1988.

Jongeneel C.V., Quackenbush E.J., Ronco P., Verroust P., Carrel S., Letarte M. Common Acute Lymphoblastic Leukemia Antigen Expressed on Leukemia and Melanoma Cell Lines Has Neutral Endopeptidase Activity. J Clin Invest. 83:713-717. 1989.

D'Adamio L., Shipp M.A., Masteller E.L., Reinherz E.L. Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions. Proc Natl Acad Sci USA. 86:7103–7107. 1989.

Belyaev N.D., Nalivaeva N.N., Makova N.Z., Turner A.J. Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease. EMBO Rep. 10:94-100. 2009.

Li C., Booze R.M., Hersh L.B. Tissue-specific expression of rat neutral endopeptidase (neprilysin) mRNAs. J Biol Chem. 270:5723–5728. 1995.

Turner A.J., Isaac R.E., Coates D. The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Bioessays. 23:261-269. 2001.

Zappulla J.P., Wickham. L., Bawab. W., Yang. X.F., Storozhuk. M.V., Castellucci. V.F., DesGroseillers. L. Cloning and characterization of Aplysia neutral endopeptidase, a metallo-endopeptidase involved in the extracellular metabolism of neuropeptides in Aplysia californica. J Neurosci. 19:4280-4292. 1999.

Shipp M.A., Richardson N.E., Sayre P.H., Brown N.R., Masteller E.L., Clayton L.K., Ritz J., Reinherz E.L. Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci U S A. 85:4819-23. 1988.

Lorkowski G., Zijderhand-Bleekemolen J.E., Erdös E.G., von Figura K., Hasilik A. Neutral endopeptidase-24.11 (enkephalinase). Biosynthesis and localization in human fibroblasts. Biochem J. 248: 345-350. 1987.

Zheng R., Horiguchi A., Iida K., Lee J., Shen R., Goodman O.B. Jr., Nanus D.M. Neutral endopeptidase is a myristoylated protein. Mol. Cell. Biochem. 335:173-180. 2010.

Ganju R.K., Shpektor R.G., Brenner D.G., Shipp M.A. CD10/neutral endopeptidase 24.11 is phosphorylated by casein kinase II and coassociates with other phosphoproteins including the lyn src-related kinase. Blood 88: 4159-4165. 1996.

Siepmann M., Kumar S., Mayer G., Walter J. Casein kinase 2 dependent phosphorylation of neprilysin regulates receptor tyrosine kinase signaling to Akt. PLoS One 5: e13134. 2010.

Bayes-Genis A., Barallat J., Richards A.M. A Test in Context: Neprilysin: Function, Inhibition, and Biomarker. J Am Coll Cardiol. 68:639-653. 2016. https://doi.org/10.1016/j.jacc.2016.04.060.

Nalivaeva N.N., Belyaev N.D., Zhuravin I.A., Turner A.J. The Alzheimer's amyloid-degrading peptidase, neprilysin: can we control it? Int J Alzheimers Dis. 2012:383796. 2012. https://doi.org/ 10.1155/2012/383796.

Nalivaeva N.N., Turner A.J. Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy. Br J Pharmacol. 176:3447-3463. 2019.

Kerr M.A., Kenny A.J. The purification and specificity of a neutral endopeptidase from rabbit kidney brush border. Biochem J. 137:477–488. 1974.

Roques B.P., Fournié-Zaluski M.C., Florentin D., Waksman G., Sassi A., Chaillet P., Collado H., Costentin J. New enkephalinase inhibitors as probes to differentiate "enkephalinase" and angiotensin-converting-enzyme active sites. Life Sci. 31:1749-1752. 1982. https://doi.org/ 10.1016/0024-3205(82)90201-6.

Komiyama T., Aoyagi T., Takeuchi T., Umezawa H. Inhibitory effects of phosphoramidon on neutral metalloendopeptidases and its application on affinity chromatography. Biochem Biophys Res Commun. 65:352-357. 1975.

Campbell D.J. Long-term neprilysin inhibition - implications for ARNIs. Nat Rev Cardiol. 14:171-186. 2017.

Rougeot C., Messaoudi M., Hermitte V., Rigault A.G., Blisnick T., Dugave C., Desor D., Rougeon F. Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity. Proc Natl Acad Sci USA. 100:8549-8554. 2003.

Wisner A., Dufour E., Messaoudi M., Nejdi A., Marcel A., Ungeheuer M.N., Rougeot C. Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc Natl Acad Sci USA. 103:17979-17984. 2006.

Barnes K., Matsas R., Hooper N.M., Turner A.J., Kenny A.J. Endopeptidase-24.11 is striosomally ordered in pig brain and, in contrast to aminopeptidase N and peptidyl dipeptidase A ('angiotensin converting enzyme') is a marker for a set of striatal efferent fibres. Neuroscience. 27:799–817. 1988.

Bourne A., Kenny A.J. The hydrolysis of brain and atrial natriuretic peptides by porcine choroid plexus is attributable to endopeptidase-24.11. Biochem J. 271:381-385. 1990. https://doi.org/ 10.1042/bj2710381.

Nalivaeva N.N., Fisk L., Kochkina E.G., Plesneva S.A., Zhuravin I.A., Babusikova E., Dobrota D., Turner A.J. Effect of hypoxia/ischemia and hypoxic preconditioning/reperfusion on expression of some amyloid-degrading enzymes. Ann N Y Acad Sci. 1035:21-33. 2004.

Barnes K., Doherty S., Turner A.J. Endopeptidase-24.11 is the integral membrane peptidase initiating degradation of somatostatin in the hippocampus. J Neurochem. 64:1826-1832. 1995.

Waksman G., Hamel E., Delay-Goyet P., Roques BP. Neuronal localization of the neutral endopeptidase 'enkephalinase' in rat brain revealed by lesions and autoradiography. EMBO J. 5:3163-3166. 1986. PMID: 3545813.

Iijima-Ando K, Hearn SA, Granger L, Shenton C, Gatt A, Chiang HC, Hakker I, Zhong Y, Iijima K. Overexpression of neprilysin reduces alzheimer amyloid-beta42 (Abeta42)-induced neuron loss and intraneuronal Abeta42 deposits but causes a reduction in cAMP-responsive element-binding protein-mediated transcription, age-dependent axon pathology, and premature death in Drosophila. J Biol Chem. 283:19066-19076. 2008.

Fukami S., Watanabe K., Iwata N., Haraoka J., Lu B., Gerard N.P., Gerard C., Fraser P., Westaway D., St George-Hyslop P., Saido T.C. Aβ-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Aβ pathology. Neurosci Res. 43:39-56. 2002.

Pacheco-Quinto J., Eckman C.B., Eckman E.A. Major amyloid-β-degrading enzymes, endothelin-converting enzyme-2 and neprilysin, are expressed by distinct populations of GABAergic interneurons in hippocampus and neocortex. Neurobiol Aging. 48:83-92. 2016. https://doi.org/ 10.1016/j.neurobiolaging.2016.08.011.

Fisk L., Nalivaeva NN, Boyle JP, Peers CS, Turner AJ. Effects of hypoxia and oxidative stress on expression of neprilysin in human neuroblastoma cells and rat cortical neurones and astrocytes. Neurochem Res. 32:1741-1748. 2007.

Shimizu E., Kawahara K., Kajizono M., Sawada M., Nakayama H. IL-4-induced selective clearance of oligomeric β-amyloid peptide1-42 by rat primary type 2 microglia. J Immunol. 181:6503-6513. 2008.

Ries M., Sastre M. Mechanisms of Aβ Clearance and Degradation by Glial Cells. Front Aging Neurosci. 8:160. 2016.

Waksman G., Hamel E., Fournié-Zaluski M.C., Roques B.P. Autoradiographic Comparison of the Distribution of the Neutral Endopeptidase "Enkephalinase" and of Mu and Delta Opioid Receptors in Rat Brain. Proc Natl Acad Sci USA. 83:1523–1527. 1986. https://doi.org/ 10.1073/pnas.83.5.1523.

Saria A., Hauser K.F., Traurig H.H., Turbek C.S., Hersh L., Gerard C. Opioid-related changes in nociceptive threshold and in tissue levels of enkephalins after target disruption of the gene for neutral endopeptidase (EC 3.4.24.11) in mice. Neurosci Lett. 234:27-30. 1997. https://doi.org/ 10.1016/s0304-3940(97)00660-5.

Barnes K., Turner A.J., Kenny A.J. An immunoelectron microscopic study of pig substantia nigra shows colocalization of endopeptidase-24.11 with substance P. Neuroscience. 53:1073-1082. 1993.

Feindt J., Krisch B., Lucius R., Mentlein R. Meningeal cells are targets and inactivation sites for the neuropeptide somatostatin. Brain Res Mol Brain Res. 44:293-300. 1997.

Nocera S., Simon A., Fiquet O., Chen Y., Gascuel J., Datiche F., Schneider N., Epelbaum J., Viollet C. Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence. Front Behav Neurosci. 13:61. 2019.

Dutriez I., Salès N., Fournié-Zaluski M.C., Roques B.P. Pre- and post-natal ontogeny of neutral endopeptidase 24-11 ('enkephalinase') studied by in vitro autoradiography in the rat. Experientia. 48:290-300. 1992.

Dauch P., Masuo Y., Vincent J.P., Checler F. A survey of the cerebral regionalization and ontogeny of eight exo- and endopeptidases in murines. Peptides. 14:593-599. 1993. https://doi.org/ 10.1016/0196-9781(93)90150-f.

Kioussi C., Crine P., Matsas R. Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve. Neuroscience. 50:69-83. 1992.

Kioussi C., Mamalaki A., Jessen K., Mirsky R., Hersh L.B., Matsas R. Expression of endopeptidase-24.11 (common acute lymphoblastic leukaemia antigen CD10) in the sciatic nerve of the adult rat after lesion and during regeneration. Eur J Neurosci. 7:951-961. 1995. https://doi.org/ 10.1111/j.1460-9568.1995.tb01083.x.

Higuchi Y., Hashiguchi A., Yuan J., Yoshimura A., Mitsui J., Ishiura H., Tanaka M., Ishihara S., Tanabe H., Nozuma S., Okamoto Y., Matsuura E., Ohkubo R., Inamizu S., Shiraishi W., Yamasaki R., Ohyagi Y., Kira J., Oya Y., Yabe H., Nishikawa N., Tobisawa S., Matsuda N., Masuda M., Kugimoto C., Fukushima K., Yano S., Yoshimura J., Doi K., Nakagawa M., Morishita S., Tsuji S., Takashima H. Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2. Ann Neurol. 79:659-672. 2016.

Maguer-Satta V., Besançon R., Bachelard-Cascales E. Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem Cells 29, 389-396. 2011. https://doi.org/ 10.1002/stem.592.

Lu B., Gerard N.P., Kolakowski L.F. Jr., Bozza M., Zurakowski D., Finco O., Carroll M.C., Gerard C. Neutral endopeptidase modulation of septic shock. J Exp Med. 181:2271–2275. 1995.

Saria A., Hauser K.F., Traurig H.H., Turbek C.S., Hersh L., Gerard C. Opioid-related changes in nociceptive threshold and in tissue levels of enkephalins after target disruption of the gene for neutral endopeptidase (EC 3.4.24.11) in mice. Neurosci Lett. 234, 27-30. 1997. https://doi.org/ 10.1016/s0304-3940(97)00660-5.

Fischer H.S., Zernig G., Schuligoi R., Miczek K.A., Hauser K.F., Gerard C., Saria A. Alterations within the endogenous opioid system in mice with targeted deletion of the neutral endopeptidase ('enkephalinase') gene. Regul Pept. 96:53-58. 2000.

Siems W., Maul B., Krause W., Gerard C., Hauser K.F., Hersh L.B., Fischer H.S., Zernig G., Saria A. Neutral endopeptidase and alcohol consumption, experiments in neutral endopeptidase-deficient mice. Eur. J. Pharmacol. 397:327-334. 2000.

Krämer HH, He L, Lu B, Birklein F, Sommer C. Increased pain and neurogenic inflammation in mice deficient of neutral endopeptidase. Neurobiol Dis. 35:177-183. 2009. https://doi.org/ 10.1016/j.nbd.2008.11.002.

Zhuravin I.A., Dubrovskaya N.M., Tumanova N.L., Vasilev D.S., Nalivaeva N.N. Ontogenetic and phylogenetic approaches for studying the mechanisms of cognitive dysfunctions. In: Evolutionary Physiology and Biochemistry: Advances and Perspectives / ed. V.F. Levchenko. InTech: Rijeka, Croatia. 2018. Chapter 15, p. 205-224. http://www.intechopen.com/books/evolutionary-physiology-andbiochemistry-advances-and-perspectives.

Dubrovskaya N.M., Zhuravin I.A. Ontogenetic characteristics of behavior in rats subjected to hypoxia on day 14 or day 18 of embryogenesis. Neurosci Behav Physiol. 40:231-238. 2010.

Nalivaeva N.N., Belyaev N.D., Lewis D.I., Pickles A.R., Makova N.Z., Bagrova D.I., Dubrovskaya N.M., Plesneva S.A., Zhuravin I.A., Turner A.J. Effect of sodium valproate administration on brain neprilysin expression and memory in rats. J Mol Neurosci. 46:569-577. 2012.

Zhuravin I.A., Dubrovskaya N.M., Vasilev D.S., Kozlova D.I., Kochkina E.G., Tumanova N.L., Nalivaeva N.N. Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia. Neurochem Res. 44:1387-1398. 2019.

Vasilev D.S., Dubrovskaya N.M., Tumanova N.L., Zhuravin I.A.. Prenatal Hypoxia in Different Periods of Embryogenesis Differentially Affects Cell Migration, Neuronal Plasticity, and Rat Behavior in Postnatal Ontogenesis. Front Neurosci. 10:126. 2016.

Deller T., Bas Orth C., Vlachos A., Merten T., Del Turco D., Dehn D., Mundel P., Frotscher M. Plasticity of synaptopodin and the spine apparatus organelle in the rat fascia dentata following entorhinal cortex lesion. J Compar Neurol. 499: 471-484. 2006. https://doi.org/ 10.1002/cne.21103.

Vasilev D.S., Tumanova N.L., Kalinina D.S. Prenatal hypoxia disturbs the formation of pyramidal neurones in the entorhinal cortex of the rat brain. Russ J Physiol. 2020. In press.

Zhang X., Li L., Zhang X., Xie W., Li L., Yang D., Heng X., Du Y., Doody R.S., Le W. Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer's disease neuropathology in APPSwe/PS1A246E transgenic mice. Neurobiol Aging. 34:663-678. 2013. https://doi.org/ 10.1016/j.neurobiolaging.2012.06.012.

Turrel O., Lampin-Saint-Amaux A., Préat T., Goguel V. Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory. J Neurosci. 36:9535-9546. 2016. https://doi.org/ 10.1523/JNEUROSCI.3730-15.

Turrel O., Rabah Y., Plaçais P.Y., Goguel V., Preat T. Drosophila Middle-Term Memory: Amnesiac is Required for PKA Activation in the Mushroom Bodies, a Function Modulated by Neprilysin 1. J Neurosci. 40:4219-4229. 2020.

Dubrovskaya N.M., Nalivaeva N.N., Plesneva S.A., Feponova A. A., Turner A.J., Zhuravin, I.A. Changes in the Activity of Amyloid-Degrading Metallopeptidases Leads to Disruption of Memory in Rats. Neurosci. Behav. Physiol. 2010. 40:975–980. https://doi.org/10.1007/s11055-010-9355-8.

Mouri A., Zou L.B., Iwata N., Saido T.C., Wang D., Wang M.W., Noda Y., Nabeshima T. Inhibition of neprilysin by thiorphan (i.c.v.) causes an accumulation of amyloid β and impairment of learning and memory. Behav Brain Res. 168:83-91. 2006.

Zhuravin I.A., Dubrovskaya N.M., Vasilev D.S., Tumanova N.L., Nalivaeva N.N. Epigenetic and pharmacological regulation of the amyloid-degrading enzyme neprilysin results in modulation of cognitive functions in mammals Dokl Biol Sci. 438:145-148. 2011. https://doi.org/ 10.1134/S001249661103015X. Epub 2011 Jul 5.

Zou L.B., Mouri A., Iwata N., Saido T.C., Wang D., Wang M.W., Mizoguchi H., Noda Y., Nabeshima T. Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory. J Pharmacol Exp Ther. 317:334-340. 2006.

Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 297:353-356. 2002.

Selkoe D.J., Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 8:595-608. 2016.

Howell S., Nalbantoglu J., Crine P. Neutral endopeptidase can hydrolyze β-amyloid (1-40) but shows no effect on β-amyloid precursor protein metabolism. Peptides 16:647-652. 1995.

Iwata N., Tsubuki S., Takaki Y., Watanabe K., Seikiguchi M., Hosoki E., Kawashima-Morishima M., Lee H.-J., Hama E., Sekine-Aizawa Y., Saido T.C. Identification of the major Aβ1-42 degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nature Med. 6:143-150. 2000.

Iwata N., Tsubuki S., Takaki Y., Shirotani K., Lu B., Gerard N.P., Gerard C., Hama E., Lee H., Saido T.C. Metabolic regulation of brain Aβ by neprilysin, Science 292:1550-1552. 2001.

Hanson LR, Hafez D, Svitak AL, Burns RB, Li X, Frey WH 2nd, Marr RA. Intranasal phosphoramidon increases beta-amyloid levels in wild-type and NEP/NEP2-deficient mice. J Mol Neurosci. 43:424-427. 2011.

Nilsson P., Loganathan K., Sekiguchi M., Winblad B., Iwata N., Saido T.C., Tjernberg L.O. Loss of neprilysin alters protein expression in the brain of Alzheimer's disease model mice. Proteomics. 15:3349-3355. 2015.

Mohajeri M.H., Wolfer D.P., Neprilysin deficiency-dependent impairment of cognitive functions in a mouse model of amyloidosis. Neurochem Res. 34:717-726. 2009. https://doi.org/ 10.1007/s11064-009-9919-6.

Carpentier M., Robitaille Y., DesGroseillers L., Boileau G., Marcinkiewicz M. Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 61:849-856. 2002.

Yasojima K., Akiyama H., McGeer E.G., McGeer P.L. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide. Neurosci Lett. 297:97-100. 2001.

Zhang H., Liu D., Wang Y., Huang H., Zhao Y., Zhou H. Meta-analysis of expression and function of neprilysin in Alzheimer's disease. Neurosci Lett 657:69-76. 2017. https://doi.org/ 10.1016/j.neulet.2017.07.060.

Li W., Wu Y., Min F., Li Z., Huang J., Huang R. A nonhuman primate model of Alzheimer's disease generated by intracranial injection of amyloid-β42 and thiorphan. Metab Brain Dis. 25:277-284. 2010.

Marr R.A., Rockenstein E., Mukherjee A., Kindy M.S., Hersh L.B., Gage F.H., Verma I.M., Masliah E. Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. J Neurosci. 23:1992-1996. 2003. PMCID: PMC6742010.

Park M.H., Lee J.K., Choi S., Ahn J., Jin H.K., Park J.S., Bae J.S. Recombinant soluble neprilysin reduces amyloid-beta accumulation and improves memory impairment in Alzheimer's disease mice. Brain Res. 1529:113-124. 2013.

Hüttenrauch M., Baches S., Gerth J., Bayer T.A., Weggen S., Wirths O. Neprilysin deficiency alters the neuropathological and behavioral phenotype in the 5XFAD mouse model of Alzheimer's disease. J Alzheimers Dis. 44:1291-1302. 2015.

Huang S.M., Mouri A., Kokubo H., Nakajima R., Suemoto T., Higuchi M., Staufenbiel M., Noda Y., Yamaguchi H., Nabeshima T., Saido T.C., Iwata N. Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function. J Biol Chem. 281:17941-17951. 2006.

Blurton-Jones M, Spencer B, Michael S, Castello NA, Agazaryan AA, Davis JL, Müller FJ, Loring JF, Masliah E, LaFerla FM. Neural stem cells genetically-modified to express neprilysin reduce pathology in Alzheimer transgenic models. Stem Cell Res Ther. 5:46. 2014.

Schliebs R., Arendt T. The cholinergic system in aging and neuronal degeneration Behav Brain Res. 221:555-563. 2011.

Foidl B.M., Do-Dinh P., Hutter-Schmid B., Bliem H.R., Humpel C. Cholinergic neurodegeneration in an Alzheimer mouse model overexpressing amyloid-precursor protein with the Swedish-Dutch-Iowa mutations. Neurobiol Learn Mem. 136:86-96. 2016. https://doi.org/ 10.1016/j.nlm.2016.09.014.

Fodero L.R., Mok S.S., Losic D., Martin L.L., Aguilar M.I., Barrow C.J., Livett, B.G., Small, D.H. Alpha7-nicotinic acetylcholine receptors mediate an Aβ(1–42)-induced increase in the level of acetylcholinesterase in primary cortical neurones. J Neurochem. 88:1186-1193.

Masliah E., Alford M., Adame A., Rockenstein E., Galasko D., Salmon D., Hansen L.A., Thal L.J. Aβ1-42 promotes cholinergic sprouting in patients with AD and Lewy body variant of AD. Neurology. 61:206-211. 2003.

Sorial M.E., El Sayed NSED. Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer's disease mouse model: possible involvement of the cholinergic system. Naunyn Schmiedebergs Arch Pharmacol. 390:581-593. 2017.

Djordjevic J., Jones-Gotman M., De Sousa K., Chertkow H. Olfaction in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging, 29:693-706. 2008. https://doi.org/ 10.1016/j.neurobiolaging.2006.11.014.

Wesson D.W., Levy E., Nixon R.A., Wilson D.A. Olfactory dysfunction correlates with amyloid-β burden in an Alzheimer's disease mouse model. J Neurosci. 30:505-514. 2010. https://doi.org/ 10.1523/JNEUROSCI.4622-09.2010.

Saiz-Sanchez D., Ubeda-Bañon I., de la Rosa-Prieto C., Argandoña-Palacios L., Garcia-Muñozguren S., Insausti R., Martinez-Marcos A. Somatostatin, Tau, and β-Amyloid Within the Anterior Olfactory Nucleus in Alzheimer Disease. Exp Neurol. 223:347-350. 2010. https://doi.org/ 10.1016/j.expneurol.2009.06.010.

Saito T., Iwata N., Tsubuki S., Takaki Y., Takano J., Huang S.M., Suemoto T., Higuchi M., Saido T.C. Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation. Nat Med. 11:434-439. 2005.

Belyaev N.D., Kellett K.A., Beckett C., Makova N.Z., Revett T.J., Nalivaeva N.N., Hooper N.M., Turner A.J. The transcriptionally active amyloid precursor protein (APP) intracellular domain is preferentially produced from the 695 isoform of APP in a β-secretase-dependent pathway. J Biol Chem. 285:41443-41454. 2010.

Pardossi-Piquard R., Petit A., Kawarai T., Sunyach C., Alves da Costa C., Vincent B., Ring S., D'Adamio L., Shen J., Müller U., St George Hyslop P., Checler F. Presenilin-dependent transcriptional control of the Aβ-degrading enzyme neprilysin by intracellular domains of βAPP and APLP. Neuron. 46:541-554. 2005.

Koudinov A.R., Berezov T.T. Alzheimer's amyloid-β (Aβ) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiol Exp (Wars). 64:71-79. 2004. PMID: 15190681.

Wang H., Megill A., He K., Kirkwood A., Lee H.K. Consequences of inhibiting amyloid precursor protein processing enzymes on synaptic function and plasticity. Neural Plast. 2012:272374. 2012.

Abramov E., Dolev I., Fogel H., Ciccotosto G.D., Ruff E., Slutsky I. Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci. 12:1567-1576. 2009.

Finnie P.S.P., Nader K. Amyloid β Secreted during Consolidation Prevents Memory Malleability. Curr Biol. 30:1934-1940.e4. 2020.

Wang Z., Zhang X.J., Li T., Li J., Tang Y., Le W. Valproic acid reduces neuritic plaque formation and improves learning deficits in APP(Swe) /PS1(A246E) transgenic mice via preventing the prenatal hypoxia-induced down-regulation of neprilysin. CNS Neurosci Ther. 20:209-217. 2014.

Janczura K.J., Volmar C.H., Sartor G.C., Rao S.J., Ricciardi N.R., Lambert G., Brothers S.P., Wahlestedt C. Inhibition of HDAC3 reverses Alzheimer's disease-related pathologies in vitro and in the 3xTg-AD mouse model. Proc Natl Acad Sci USA. 115:E11148-E11157. 2018.

Hu Q., Chang X., Yan R., Rong C., Yang C., Cheng S., Gu X., Yao H., Hou X., Mo Y., Zhao L., Chen Y., Dinlin X., Wang Q., Fang S. (−)-Epigallocatechin-3-gallate induces cancer cell apoptosis via acetylation of amyloid precursor protein. Med Oncol. 32: 390. 2015. https://doi.org/ 10.1007/s12032-014-0390-0.

Chang X., Rong C., Chen Y., Yang C., Hu Q., Mo Y., Zhang C., Gu X., Zhang L., He W., Cheng S., Hou X., Su R., Liu S., Dun W., Wang Q., Fang S. (-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression. Exp Cell Res. 334:136-145. 2015.

Kerridge C., Kozlova D.I., Nalivaeva N.N., Turner A.J. Hypoxia Affects Neprilysin Expression Through Caspase Activation and an APP Intracellular Domain-dependent Mechanism. Front Neurosci. 9:426. 2015.

Vasilev D. S., Dubrovskaya N. M., Nalivaeva N. N., Zhuravin I. A. 2016. Regulation of caspase-3 content and activity in rat cortex in norm and after prenatal hypoxia. Neurochem J. 10:144–150.

Kozlova D.I., Vasylev D.S., Dubrovskaya N.M., Nalivaeva N.N., Tumanova N.L., Zhuravin I.A. Role of caspase-3 in regulation of the amyloid-degrading neuropeptidase neprilysin level in the rat cortex after hypoxia. J. Evol. Biochem. Physiol. 51:480-484. 2015. https://doi.org/ 10.1134/S0022093015060046.

Dubrovskaya N.M., Tikhonravov D.L., Alekseeva O.S., Zhuravin I.A. Recovery of learning and memory impaired by prenatal hypoxic stress in rats after injection of caspase-3 inhibitor during early ontogenesis // Journal of Evolutionary Biochemistry and Physiology. 53(1):66-68. 2017.

Nalivaeva N.N., Belyaev N.D., Turner A.J. New Insights into Epigenetic and Pharmacological Regulation of Amyloid-Degrading Enzymes. Neurochem Res. 41:620-630. 2016.

Dubrovskaya N.M., Vasilev D.S., Nalivaeva N.N., Tumanova N.L., Alekseeva O.S., Zhuravin I.A. Bexarotene, an Agonist of Nuclear X Retinoid Receptors, Improves Cognitive Functions in Rats Subjected to Prenatal Hypoxia. Russ J Physiol. 105:165-177. 2019. (Article in Russian).

Sandoval K.E., Farr S.A., Banks W.A., Crider A.M., Morley J.E., Witt K.A. Somatostatin receptor subtype-4 agonist NNC 26-9100 decreases extracellular and intracellular Aβ₁₋₄₂ trimers. Eur J Pharmacol. 683:116-124. 2012.

Klein C., Roussel G., Brun S., Rusu C., Patte-Mensah C., Maitre M., Mensah-Nyagan A.G. 5-HIAA induces neprilysin to ameliorate pathophysiology and symptoms in a mouse model for Alzheimer's disease. Acta Neuropathol Commun. 6:136. 2018.

Yu L., Liu Y., Yang H., Zhu X., Cao X., Gao J., Zhao H., Xu Y. PSD-93 Attenuates Amyloid-β-Mediated Cognitive Dysfunction by Promoting the Catabolism of Amyloid-β. J Alzheimers Dis. 59:913-927. 2017.

Lazarov O., Robinson J., Tang Y.P., Hairston I.S., Korade-Mirnics Z., Lee V.M., Hersh L.B., Sapolsky R.M., Mirnics K., Sisodia S.S. Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell. 120:701-713. 2005.

Griva M., Lagoudaki R., Touloumi O., Nousiopoulou E., Karalis F., Georgiou T., Kokaraki G., Simeonidou C., Tata D.A., Spandou E. Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined treatment with G-CSF Brain Res. 1667:55-67. 2017.

Radak Z., Kumagai S., Taylor A.W., Naito H., Goto S. Effects of exercise on brain function: role of free radicals. Appl Physiol Nutr Metab. 32:942-946. 2007.

Mainardi M., Di Garbo A., Caleo M., Berardi N., Sale A., Maffei L. Environmental enrichment strengthens corticocortical interactions and reduces amyloid-β oligomers in aged mice. Front Aging Neurosci. 6:1. 2014.

Walther T., Albrecht D., Becker M., Schubert M., Kouznetsova E., Wiesner B., Maul B., Schliebs R., Grecksch G., Furkert J., Sterner-Kock A., Schultheiss H.P., Becker A., Siems W.E. Improved learning and memory in aged mice deficient in amyloid β-degrading neutral endopeptidase. PLoS One. 4:e4590. 2009.

Saito T., Takaki Y., Iwata N., Trojanowski J., Saido T.C. Alzheimer's disease, neuropeptides, neuropeptidase, and amyloid-β peptide metabolism Sci Aging Knowledge Environ. 2003:PE1. 2003.