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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Nf-κb: A Target for Synchronizing the Functioning Nervous Tissue Progenitors of Different Types in Alzheimer's Disease

Author(s): Gleb Nikolaevich Zyuz’kov*, Larisa Arkad’evna Miroshnichenko, Alexander Vasil’evich Chayikovskyi and Larisa Yur’evna Kotlovskaya

Volume 16, Issue 2, 2023

Published on: 21 July, 2022

Article ID: e010622205529 Pages: 8

DOI: 10.2174/1874467215666220601144727

Price: $65

Abstract

Background: The efficacy of Alzheimer's disease (AD) treatment can be enhanced by developing neurogenesis regulation approaches by synchronizing regenerative-competent cell (RCCs) activity. As part of the implementation of this direction, the search for drug targets among intracellular signaling molecules is promising.

Objective: This study aims to test the hypothesis that NF-кB inhibitors are able to synchronize the activities of different types RCCs in AD.

Methods: The effects of NF-κB inhibitor JSH-23 on the functioning of neural stem cells (NSCs), neuronal-committed progenitors (NCPs), and neuroglial cells were studied. Individual populations of C57B1/6 mice brain cells were obtained by immunomagnetic separation. Studies were carried out under conditions of modeling β-amyloid-induced neurodegeneration (βAIN) in vitro.

Results: We showed that β-amyloid (Aβ) causes divergent changes in the functioning of NSCs and NCPs. Also demonstrated that different populations of neuroglia respond differently to exposure to Aβ. These phenomena indicate a significant discoordination of the activities of various RCCs. We revealed an important role of NF-κB in the regulation of progenitor proliferation and differentiation and glial cell secretory function. It was found that the NF-κB inhibitor causes synchronization of the pro-regenerative activities of NSCs, NCPs, as well as oligodendrocytes and microglial cells in βAIN.

Conclusion: The results show the promise of developing a novel approach to Alzheimer's disease treatment with NF-κВ inhibitors.

Keywords: Alzheimer's disease, stem cells, glial cells, neurodegenerative diseases, NF-кB, signaling molecules.

Graphical Abstract

[1]
Drummond, E.; Pires, G.; MacMurray, C.; Askenazi, M.; Nayak, S.; Bourdon, M.; Safar, J.; Ueberheide, B.; Wisniewski, T. Phosphorylated tau interactome in the human Alzheimer’s disease brain. Brain, 2020, 143(9), 2803-2817.
[http://dx.doi.org/10.1093/brain/awaa223] [PMID: 32812023]
[2]
Han, F.; Bi, J.; Qiao, L.; Arancio, O. Stem cell therapy for alzheimer’s disease. Adv. Exp. Med. Biol., 2020, 1266, 39-55.
[http://dx.doi.org/10.1007/978-981-15-4370-8_4] [PMID: 33105494]
[3]
Wang, Z.; Chen, Y.; Li, X.; Sultana, P.; Yin, M.; Wang, Z. Amyloid-β1-42 dynamically regulates the migration of neural stem/progenitor cells via MAPK-ERK pathway. Chem. Biol. Interact., 2019, 298, 96-103.
[http://dx.doi.org/10.1016/j.cbi.2018.11.001] [PMID: 30399361]
[4]
Ozben, T.; Ozben, S. Neuro-inflammation and anti-inflammatory treatment options for Alzheimer’s disease. Clin. Biochem., 2019, 72, 87-89.
[http://dx.doi.org/10.1016/j.clinbiochem.2019.04.001]
[5]
Udut, V.V.; Naumov, S.A.; Evtushenko, D.N.; Udut, E.V.; Naumov, S.S.; Zyuz’kov, G.N. A case of xenon inhalation therapy for respiratory failure and neuropsychiatric disorders associated with COVID-19. EXCLI J., 2021, 20, 1517-1525.
[http://dx.doi.org/10.17179/excli2021-4316] [PMID: 34924901]
[6]
Kaeser, G.; Chun, J. Brain cell somatic gene recombination and its phylogenetic foundations. J. Biol. Chem., 2020, 295(36), 12786-12795.
[http://dx.doi.org/10.1074/jbc.REV120.009192] [PMID: 32699111]
[7]
Gallardo, G.; Holtzman, D.M. Amyloid-β and Tau at the Crossroads of Alzheimer’s Disease. Adv. Exp. Med. Biol., 2019, 1184, 187-203.
[http://dx.doi.org/10.1007/978-981-32-9358-8_16] [PMID: 32096039]
[8]
Coronel, R.; Lachgar, M.; Bernabeu-Zornoza, A.; Palmer, C.; Domínguez-Alvaro, M.; Revilla, A.; Ocaña, I.; Fernández, A.; Martínez-Serrano, A.; Cano, E.; Liste, I. Neuronal and glial differentiation of human neural stem cells is regulated by Amyloid Precursor Protein (APP) levels. Mol. Neurobiol., 2019, 56(2), 1248-1261.
[http://dx.doi.org/10.1007/s12035-018-1167-9] [PMID: 29881946]
[9]
Mihardja, M.; Roy, J.; Wong, K.Y.; Aquili, L.; Heng, B.C.; Chan, Y.S.; Fung, M.L.; Lim, L.W. Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer’s disease. Ann. N. Y. Acad. Sci., 2020, 1478(1), 43-62.
[http://dx.doi.org/10.1111/nyas.14436] [PMID: 32700392]
[10]
Sung, P.S.; Lin, P.Y.; Liu, C.H.; Su, H.C.; Tsai, K.J. Neuroinflammation and neurogenesis in alzheimer’s disease and potential therapeutic approaches. Int. J. Mol. Sci., 2020, 21(3), 701.
[http://dx.doi.org/10.3390/ijms21030701] [PMID: 31973106]
[11]
Zyuz’kov, G.N. Targeted regulation of intracellular signal transduc-tion in regenerative-competent cells: A new direction for therapy in regenerative medicine. Biointerface Res. Appl. Chem., 2021, 11(4), 12238-12251.
[http://dx.doi.org/10.33263/BRIAC114.1223812251]
[12]
Zyuz’kov, G.N.; Arkad Evna, L.; Polykova, T.Y.E.; Simanina, E.V.; Stavrova, L.A. Targeting cAMP-pathway in regeneration-competent cells of nervous tissue: Potential to create a novel drug for treatment of ethanol-induced neurodegeneration. Cent. Nerv. Syst. Agents Med. Chem., 2021, 21(3), 172-180.
[http://dx.doi.org/10.2174/1871524921666210907102847] [PMID: 34493198]
[13]
Zyuz’kov, G.N.; Miroshnichenko, L.A.; Polyakova, T.Yu.; Stavrova, L.A.; Simanina, E.V. Inhibition of adenylate cyclase of regenerationcompetent cells of nervous tissue: A novel approach for the treatment of alcoholic encephalopathy. Biointerface Res. Appl. Chem., 2022, 12(2), 1547-1560.
[http://dx.doi.org/10.33263/BRIAC122.15471560]
[14]
Zyuz’kov, G.N.; Stavrova, L.A.; Miroshnichenko, L.A.; Polyakova, T.Yu.; Simanina, E.V. Prospects for the Use of NF-кb inhibitors to stimulate the functions of regenerative-competent cells of nerve tissue and neuroregeneration in ethanol-induced neurodegeneration. Biointerface Res. Appl. Chem., 2021, 11(1), 8065-8074.
[http://dx.doi.org/10.33263/BRIAC111.80658074]
[15]
Zyuz’kov, G.N.; Miroshnichenko, L.A.; Polyakova, T.Yu.; Zhdanov, V.V.; Simanina, E.V.; Stavrova, L.A.; Churin, A.A.; Fomina, T.I. Role of MAPK ERK1/2 and p38 in the regulation of secretory functions of different populations of neuroglia in ethanol-induced neurodegeneration. Bull. Exp. Biol. Med., 2021, 171(6), 699-703.
[http://dx.doi.org/10.1007/s10517-021-05298-x] [PMID: 34709510]
[16]
Zyuz’kov, G.N.; Miroshnichenko, L.A.; Simanina, E.V.; Stavrova, L.A.; Polyakova, T.Yu. .Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanolinduced neurodegeneration. J. Basic Clin. Physiol. Pharmacol, 2021, 32JBCPP-2020-0317.
[http://dx.doi.org/10.1515/jbcpp-2020-0317]
[17]
Hossain, M.F.; Uddin, M.S.; Uddin, G.M.S.; Sumsuzzman, D.M.; Islam, M.S.; Barreto, G.E.; Mathew, B.; Ashraf, G.M. Melatonin in alzheimer’s disease: A latent endogenous regulator of neurogenesis to mitigate alzheimer’s neuropathology. Mol. Neurobiol., 2019, 56(12), 8255-8276.
[http://dx.doi.org/10.1007/s12035-019-01660-3] [PMID: 31209782]
[18]
Bae, T.; Tomasini, L.; Mariani, J.; Zhou, B.; Roychowdhury, T.; Franjic, D.; Pletikos, M.; Pattni, R.; Chen, B.J.; Venturini, E.; Riley-Gillis, B.; Sestan, N.; Urban, A.E.; Abyzov, A.; Vaccarino, F.M. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science, 2018, 359(6375), 550-555.
[http://dx.doi.org/10.1126/science.aan8690] [PMID: 29217587]
[19]
Lee, M.H.; Siddoway, B.; Kaeser, G.E.; Segota, I.; Rivera, R.; Romanow, W.J.; Liu, C.S.; Park, C.; Kennedy, G.; Long, T.; Chun, J. Somatic APP gene recombination in Alzheimer’s disease and normal neurons. Nature, 2018, 563(7733), 639-645.
[http://dx.doi.org/10.1038/s41586-018-0718-6] [PMID: 30464338]
[20]
Vaz, M.; Silvestre, S. Alzheimer’s disease: Recent treatment strategies. Eur. J. Pharmacol., 2020, 887, 173554.
[http://dx.doi.org/10.1016/j.ejphar.2020.173554] [PMID: 32941929]
[21]
Bernabeu-Zornoza, A.; Coronel, R.; Lachgar, M.; Palmer, C.; Liste, I. Effects of amyloid-β peptide on the biology of human neural stem cells. Methods Mol. Biol., 2018, 1779, 381-398.
[http://dx.doi.org/10.1007/978-1-4939-7816-8_23] [PMID: 29886545]
[22]
Singh, S.; Singh, T.G. Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: An mechanistic approach. Curr. Neuropharmacol., 2020, 18(10), 918-935.
[http://dx.doi.org/10.2174/1570159X18666200207120949] [PMID: 32031074]
[23]
Thawkar, B.S.; Kaur, G. Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. J. Neuroimmunol., 2019, 326, 62-74.
[http://dx.doi.org/10.1016/j.jneuroim.2018.11.010] [PMID: 30502599]
[24]
Jha, N.K.; Jha, S.K.; Kar, R.; Nand, P.; Swati, K.; Goswami, V.K. Nuclear factor-kappa β as a therapeutic target for Alzheimer’s disease. J. Neurochem., 2019, 150(2), 113-137.
[http://dx.doi.org/10.1111/jnc.14687] [PMID: 30802950]
[25]
Hwang, J.C.; Choi, D.Y.; Park, M.H.; Hong, J.T. NF-kappaB as a Key Mediator of Brain Inflammation in Alzheimer’s Disease. CNS Neurol. Disord. Drug Targets, 2019, 18, 3-10.
[http://dx.doi.org/10.2174/1871527316666170807130011] [PMID: 28782486]
[26]
Curtis, M.J.; Bond, R.A.; Spina, D.; Ahluwalia, A.; Alexander, S.P.; Giembycz, M.A.; Gilchrist, A.; Hoyer, D.; Insel, P.A.; Izzo, A.A.; Lawrence, A.J.; MacEwan, D.J.; Moon, L.D.; Wonnacott, S.; Weston, A.H.; McGrath, J.C. Experimental design and analysis and their reporting: New guidance for publication in BJP. Br. J. Pharmacol., 2015, 172(14), 3461-3471.
[http://dx.doi.org/10.1111/bph.12856] [PMID: 26114403]
[27]
Hu, Z.; Deng, N.; Liu, K.; Zhou, N.; Sun, Y.; Zeng, W. CNTFSTAT3-IL-6 axis mediates neuroinflammatory cascade across schwann cell-neuron-microglia. Cell Rep., 2020, 31(7), 107657.
[http://dx.doi.org/10.1016/j.celrep.2020.107657] [PMID: 32433966]
[28]
Lu, J.; Li, Y.; Mollinari, C.; Garaci, E.; Merlo, D.; Pei, G. Amyloid-β oligomers-induced mitochondrial dna repair impairment contributes to altered human neural stem cell differentiation. Curr. Alzheimer Res., 2019, 16(10), 934-949.
[http://dx.doi.org/10.2174/1567205016666191023104036] [PMID: 31642778]
[29]
Hayashi, Y.; Lin, H.T.; Lee, C.C.; Tsai, K.J. Effects of neural stem cell transplantation in Alzheimer’s disease models. J. Biomed. Sci., 2020, 27(1), 29.
[http://dx.doi.org/10.1186/s12929-020-0622-x] [PMID: 31987051]
[30]
Kronenberg, J.; Merkel, L.; Heckers, S.; Gudi, V.; Schwab, M.H.; Stangel, M. Investigation of neuregulin-1 and glial cell-derived neurotrophic factor in rodent astrocytes and microglia. J. Mol. Neurosci., 2019, 67(3), 484-493.
[http://dx.doi.org/10.1007/s12031-019-1258-8] [PMID: 30680593]

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