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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

MicroRNA-125a-3p Modulate Amyloid β-Protein through the MAPK Pathway in Alzheimer’s Disease

Author(s): Xi-Chen Zhu*, Meng-Zhuo Zhu, Jing Lu, Qing-Yu Yao, Jia-Wei Hu, Wen-Jun Long, Sha-Sha Ruan, Wen-Zhuo Dai and Rong Li*

Volume 20, Issue 7, 2023

Published on: 22 September, 2023

Page: [471 - 480] Pages: 10

DOI: 10.2174/1567205020666230913105811

Price: $65

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Abstract

Background: MicroRNA (miR)-125a-3p is reported to play an important role in some central nervous system diseases, such as Alzheimer’s disease (AD). However, a study has not been conducted on the mechanism of miR-125a-3p in the pathological process of AD.

Methods: First, we assessed the expression of miR-125a-3p in AD cohort. Subsequently, we altered the expressions of miR-125a-3p to assess its role in cell viability, cell apoptosis, amyloid-β (Aβ) metabolism, and synaptic activity. Finally, we identified its potential mechanism underlying AD pathology.

Results: This study unveiled the potential function of miR-125a-3p through modulating amyloid precursor protein processing. Additionally, miR-125a-3p influenced cell survival and activated synaptic expression through the modulation of Aβ metabolism in the mitogen-activated protein kinase (MAPK) pathway via fibroblast growth factor receptor 2.

Conclusion: Our study indicates that targeting miR-125a-3p may be an applicable therapy for AD in the future. However, more in vitro and in vivo studies with more samples are needed to confirm these results.

Keywords: Alzheimer’s disease, miR-125a-3p, Aβ, fibroblast growth factor receptor 2, MAPK pathway, MicroRNA.

« Previous Next »
[1]
Sengoku, R. Aging and Alzheimer’s disease pathology. Neuropathology, 2020, 40(1), 22-29.
[http://dx.doi.org/10.1111/neup.12626] [PMID: 31863504]
[2]
a) Han, B.; Chao, J.; Yao, H. Circular RNA and its mechanisms in disease: From the bench to the clinic. Pharmacol Ther., 2018, 187, 31-44.;
b) Doxtater, K.; Tripathi, M.K.; Khan, M.M. Recent advances on the role of long non-coding RNAs in Alzheimer’s disease. Neural Regen. Res., 2020, 15(12), 2253-2254.
[3]
(a) Cieslik, M.; Czapski, G.A.; Wojtowicz, S.; Wieczorek, I.; Wencel, P.L.; Strosznajder, R.P. Alterations of Transcription of Genes Coding Anti-oxidative and Mitochondria-Related Proteins in Amyloid beta Toxicity: Relevance to Alzheimer’s Disease. Mol Neurobiol., 2020, 57(3), 1374-88;
(b) Zolochevska, O.; Taglialatela, G. Selected microRNAs increase synaptic resilience to the damaging binding of the Alzheimer’s disease amyloid beta oligomers. Mol Neurobiol., 2020, 57(5), 2232-43;
(c) Brito, L.M.; Ribeiro-Dos-Santos, A.; Vidal, A.F.; de Araujo, G.S. Differential Expression and miRNA-Gene Interactions in early and late mild cognitive impairment. Biology (Basel), 2020, 9(9)
[4]
McKeever, PM; Schneider, R; Taghdiri, F; Weichert, A; Multani, N; Brown, RA MicroRNAs in human cerebrospinal fluid as biomarkers for Alzheimer's disease. J. Alzheimers Dis., 2017, 55(3), 1223-1233.
[PMID: 27814298]
[5]
Wu, HZY; Thalamuthu, A; Cheng, L; Fowler, C; Masters, CL; Sachdev, P MicroRNA expression signature in mild cognitive impairment due to Alzheimer's disease. Mol. Neurobiol., 2020, 57(11), 4408-4416.
[http://dx.doi.org/10.1007/s12035-020-02029-7] [PMID: 32737762]
[6]
Wang, WX; Rajeev, BW; Stromberg, AJ; Ren, N; Tang, G; Huang, Q miR-34a knockout attenuates cognitive deficits in APP/PS1 mice through inhibition of the amyloidogenic processing of APP. Life Sci., 2017, 182, 104-111.
[http://dx.doi.org/10.1016/j.lfs.2017.05.023] [PMID: 28533191]
[7]
(a) Smith, P.Y.; Hernandez-Rapp, J.; Jolivette, F.; Lecours, C.; Bisht, K.; Goupil, C. miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo. Hum Mol Genet, 2015, 24(23), 6721-35;
(b) Dickson, J.R.; Kruse, C.; Montagna, D.R.; Finsen, B.; Wolfe, M.S. Alternative polyadenylation and miR-34 family members regulate tau expression. J. Neurochem., 2013, 127(6), 739-749.
[PMID: 24032460]
[8]
Yin, F.; Zhang, J.N.; Wang, S.W.; Zhou, C.H.; Zhao, M.M.; Fan, W.H.; Fan, M.; Liu, S. MiR-125a-3p regulates glioma apoptosis and invasion by regulating Nrg1. PLoS One, 2015, 10(1), e0116759.
[http://dx.doi.org/10.1371/journal.pone.0116759] [PMID: 25560389]
[9]
Marangon, D.; Boda, E.; Parolisi, R.; Negri, C.; Giorgi, C.; Montarolo, F.; Perga, S.; Bertolotto, A.; Buffo, A.; Abbracchio, M.P.; Lecca, D. In vivo silencing of miR-125a-3p promotes myelin repair in models of white matter demyelination. Glia, 2020, 68(10), 2001-2014.
[http://dx.doi.org/10.1002/glia.23819] [PMID: 32163190]
[10]
Zhao, Y.Y.; Wang, W.A.; Hu, H. Treatment with recombinant tissue plasminogen activator alters the microRNA expression profiles in mouse brain after acute ischemic stroke. Neurol. Sci., 2015, 36(8), 1463-1470.
[http://dx.doi.org/10.1007/s10072-015-2149-6] [PMID: 25809569]
[11]
Chen, W.; Wu, L.; Hu, Y.; Jiang, L.; Liang, N.; Chen, J.; Qin, H.; Tang, N. MicroRNA-107 ameliorates damage in a cell model of Alzheimer’s disease by mediating the FGF7/FGFR2/PI3K/Akt pathway. J. Mol. Neurosci., 2020, 70(10), 1589-1597.
[http://dx.doi.org/10.1007/s12031-020-01600-0] [PMID: 32472396]
[12]
Pfaff, M.J.; Xue, K.; Li, L.; Horowitz, M.C.; Steinbacher, D.M.; Eswarakumar, J.V.P. FGFR2c-mediated ERK–MAPK activity regulates coronal suture development. Dev. Biol., 2016, 415(2), 242-250.
[http://dx.doi.org/10.1016/j.ydbio.2016.03.026] [PMID: 27034231]
[13]
Nguyen, M.B.; Valdes, V.J.; Cohen, I.; Pothula, V.; Zhao, D.; Zheng, D.; Ezhkova, E. Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR 2-mediated signalling. Exp. Dermatol., 2019, 28(4), 374-382.
[http://dx.doi.org/10.1111/exd.13901] [PMID: 30758073]
[14]
Xu, L.; Li, J.; Luo, Z.; Wu, Q.; Fan, W.; Yao, X.; Li, Q.; Yan, H.; Wang, J. Aβ inhibits mesenchymal stem cell–pericyte transition through MAPK pathway. Acta Biochim. Biophys. Sin. (Shanghai), 2018, 50(8), 776-781.
[http://dx.doi.org/10.1093/abbs/gmy072] [PMID: 29939221]
[15]
Falcicchia, C.; Tozzi, F.; Arancio, O.; Watterson, D.M.; Origlia, N. Involvement of p38 MAPK in synaptic function and dysfunction. Int. J. Mol. Sci., 2020, 21(16), 5624.
[http://dx.doi.org/10.3390/ijms21165624] [PMID: 32781522]
[16]
Kheiri, G.; Dolatshahi, M.; Rahmani, F.; Rezaei, N. Role of p38/MAPKs in Alzheimer’s disease: Implications for amyloid beta toxicity targeted therapy. Rev. Neurosci., 2018, 30(1), 9-30.
[http://dx.doi.org/10.1515/revneuro-2018-0008] [PMID: 29804103]
[17]
Tamaoka, A. Alzheimer’s disease: Definition and national institute of neurological and communicative disorders and stroke and the Alzheimer’s disease and related disorders association (NINCDS-ADRDA). Jpn. J. Clin. Med., 2011, 69(Suppl. 10 Pt 2), 240-245.
[PMID: 22755191]
[18]
Zhao, Z.Y.; Zhang, Y.Q.; Zhang, Y.H.; Wei, X.Z.; Wang, H.; Zhang, M.; Yang, Z.J.; Zhang, C.H. The protective underlying mechanisms of Schisandrin on SH-SY5Y cell model of Alzheimer’s disease. J. Toxicol. Environ. Health A, 2019, 82(19), 1019-1026.
[http://dx.doi.org/10.1080/15287394.2019.1684007] [PMID: 31739764]
[19]
Lu, L.; Dai, W.Z.; Zhu, X.C.; Ma, T. Analysis of serum miRNAs in Alzheimer’s disease. Am. J. Alzheimers Dis. Other Demen., 2021, 36, 15333175211021712.
[http://dx.doi.org/10.1177/15333175211021712] [PMID: 34080437]
[20]
Kumar, S.; Reddy, A.P.; Yin, X.; Reddy, P.H. miRNAs in Alzheimer disease - A therapeutic perspective. Curr. Alzheimer Res., 2017, 14(11), 1198-1206.
[PMID: 28847283]
[21]
Sun, Y.M.; Lin, K.Y.; Chen, Y.Q. Diverse functions of miR-125 family in different cell contexts. J. Hematol. Oncol., 2013, 6(1), 6.
[http://dx.doi.org/10.1186/1756-8722-6-6] [PMID: 23321005]
[22]
Lecca, D.; Marangon, D.; Coppolino, G.T.; Méndez, A.M.; Finardi, A.; Costa, G.D.; Martinelli, V.; Furlan, R.; Abbracchio, M.P. MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. Sci. Rep., 2016, 6(1), 34503.
[http://dx.doi.org/10.1038/srep34503] [PMID: 27698367]
[23]
Nunomura, A; Perry, G. Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer's disease. Alzheimers Res. Ther., 2020, 12(1), 163.
[http://dx.doi.org/10.1186/s13195-020-00735-x] [PMID: 33278902]
[24]
a) Lee, M.; Kang, Y.; Suk, K.; Schwab, C.; Yu, S.; McGeer, P.L. Acidic fibroblast growth factor (FGF) potentiates glial-mediated neurotoxicity by activating FGFR2 IIIb protein. J Biol Chem, 2011, 286(48), 41230-45;
b) Caceres, A.; Gonzalez, J.R. When pitch adds to volume: Coregulation of transcript diversity predicts gene function. BMC Genomics, 2018, 19(1), 926.
[PMID: 30545302]
[25]
Schnöder, L.; Gasparoni, G.; Nordström, K.; Schottek, A.; Tomic, I.; Christmann, A.; Schäfer, K.H.; Menger, M.D.; Walter, J.; Fassbender, K.; Liu, Y. Neuronal deficiency of p38α-MAPK ameliorates symptoms and pathology of APP or Tau-transgenic Alzheimer’s mouse models. FASEB J., 2020, 34(7), 9628-9649.
[http://dx.doi.org/10.1096/fj.201902731RR] [PMID: 32475008]
[26]
Leugers, C.J.; Koh, J.Y.; Hong, W.; Lee, G. Tau in MAPK Activation. Front. Neurol., 2013, 4, 161.
[http://dx.doi.org/10.3389/fneur.2013.00161] [PMID: 24146661]
[27]
Lee, J.K.; Kim, N.J. Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer’s disease. Molecules, 2017, 22(8), 1287.
[http://dx.doi.org/10.3390/molecules22081287] [PMID: 28767069]
[28]
Plastira, I.; Bernhart, E.; Joshi, L.; Koyani, C.N.; Strohmaier, H.; Reicher, H.; Malle, E.; Sattler, W. MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia. J. Neuroinflammation, 2020, 17(1), 127.
[http://dx.doi.org/10.1186/s12974-020-01809-1] [PMID: 32326963]
[29]
a) Mattson, M.P. Calcium and neuronal injury in Alzheimer’s disease. Contributions of beta-amyloid precursor protein mismetabolism, free radicals, and metabolic compromise. Ann N Y Acad Sci., 1994, 747, 50-76;
b) Calkins, M.J.; Reddy, P.H. Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer’s disease neurons. Biochim. Biophys. Acta, 2011, 1812(4), 507-513.
[PMID: 21241801]
[30]
Dong, Y.; Li, P.; Ni, Y.; Zhao, J.; Liu, Z. Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain. PLoS One, 2014, 9(11), e111594.
[http://dx.doi.org/10.1371/journal.pone.0111594] [PMID: 25380251]

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