Neuroprotective Effect of Osthole on Neuron Synapses in an Alzheimer's Disease Cell Model Via Upregulation of MicroRNA-9

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2016 Jul 11

PMID 27394443

Citations 27

Authors

Shaoheng Li

Yuhui Yan

Yanan Jiao

Zhong Gao

Yang Xia

Liang Kong

Yingjia Yao

Zhenyu Tao

Jie Song

Yaping Yan

Guangxian Zhang

Jingxian Yang

Affiliations

Soon will be listed here.

Abstract

Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). It has been reported that osthole exerts its neuroprotective effect on neuronal synapses, but its exact mechanism is obscure. Recently, microRNAs have been demonstrated to play a crucial role in inducing synaptotoxicity by Aβ, implying that targeting microRNAs could be a therapeutic approach of AD. In the present study, we investigated the neuroprotective effects of osthole on a cell model of AD by transducing APP695 Swedish mutant (APP695swe, APP) into mouse cortical neurons and human SH-SY5Y cells. In this study, the cell counting kit CCK-8, apoptosis assay, immunofluorescence analysis, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction, and Western blot assay were used. We found that osthole could enhance cell viability, prevent cell death, and reverse the reduction of synaptic proteins (synapsin-1, synaptophysin, and postsynaptic density-95) in APP-overexpressed cells, which was attributed to increases in microRNA-9 (miR-9) expression and subsequent decreases in CAMKK2 and p-AMPKα expressions. These results demonstrated that osthole plays a neuroprotective activity role in part through upregulating miR-9 in AD.

Citing Articles

Rodent Model of Cardiopulmonary Bypass Demonstrates Systemic Inflammation and Neuromarker Changes.

Zhang A, Haywood N, Money D, Byler M, Osuru H, Atluri N J Surg Res. 2024; 303:780-787.

PMID: 39471762 PMC: 11602341. DOI: 10.1016/j.jss.2024.09.041.

Inhibition of Glycogen Synthase Kinase and the Neuroprotective Function of Conjugated ZnO-Osthol Nanoparticles in Alzheimer's Disease.

Alharthi N, Aldakheel F, Binshaya A Bioinorg Chem Appl. 2024; 2022:1401995.

PMID: 39281976 PMC: 11401704. DOI: 10.1155/2022/1401995.

Noncoding RNAs in Alzheimer's Disease: Overview of Functional and Therapeutic Significance.

Adiga D, Eswaran S, Srinath S, Khan N, Kumar D, Kabekkodu S Curr Top Med Chem. 2024; 24(19):1615-1634.

PMID: 38616763 DOI: 10.2174/0115680266293212240405042540.

miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer's disease.

Han S, Pyun J, Bice P, Bennett D, Saykin A, Kim S Alzheimers Res Ther. 2024; 16(1):5.

PMID: 38195609 PMC: 10775662. DOI: 10.1186/s13195-023-01366-8.

Identification of Molecular Mechanisms Responsible for the MMP-9-1562C/T Dependent Differential Regulation of Matrix Metalloproteinase-9 Expression in Human Neuron-like Cells.

Pabian-Jewula S, Ambrozek-Latecka M, Bragiel-Pieczonka A, Nowicka K, Rylski M Genes (Basel). 2023; 14(11).

PMID: 38002971 PMC: 10671763. DOI: 10.3390/genes14112028.

References

Stein S, Woods A, Jones N, Davison M, Carling D . The regulation of AMP-activated protein kinase by phosphorylation. Biochem J. 2000; 345 Pt 3:437-43. PMC: 1220775. View

Che H, Sun L, Guo F, Niu H, Su X, Bao Y . Expression of amyloid-associated miRNAs in both the forebrain cortex and hippocampus of middle-aged rat. Cell Physiol Biochem. 2014; 33(1):11-22. DOI: 10.1159/000356646. View

Heredia L, Helguera P, de Olmos S, Kedikian G, Sola Vigo F, LaFerla F . Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease. J Neurosci. 2006; 26(24):6533-42. PMC: 6674046. DOI: 10.1523/JNEUROSCI.5567-05.2006. View

Mairet-Coello G, Courchet J, Pieraut S, Courchet V, Maximov A, Polleux F . The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Aβ oligomers through Tau phosphorylation. Neuron. 2013; 78(1):94-108. PMC: 3784324. DOI: 10.1016/j.neuron.2013.02.003. View

Delay C, Mandemakers W, Hebert S . MicroRNAs in Alzheimer's disease. Neurobiol Dis. 2012; 46(2):285-90. DOI: 10.1016/j.nbd.2012.01.003. View

Yang J, Yan Y, Xia Y, Kang T, Li X, Ciric B . Neurotrophin 3 transduction augments remyelinating and immunomodulatory capacity of neural stem cells. Mol Ther. 2013; 22(2):440-450. PMC: 3918915. DOI: 10.1038/mt.2013.241. View

Chen C, Li L, Lodish H, Bartel D . MicroRNAs modulate hematopoietic lineage differentiation. Science. 2003; 303(5654):83-6. DOI: 10.1126/science.1091903. View

Liu Q, Vera Chang M, Lei J, Koukiekolo R, Smith B, Zhang D . Identification of microRNAs involved in Alzheimer's progression using a rabbit model of the disease. Am J Neurodegener Dis. 2014; 3(1):33-44. PMC: 3986609. View

Wang J, Gu Z, Ni P, Qiao Y, Chen C, Liu X . NF-kappaB P50/P65 hetero-dimer mediates differential regulation of CD166/ALCAM expression via interaction with micoRNA-9 after serum deprivation, providing evidence for a novel negative auto-regulatory loop. Nucleic Acids Res. 2011; 39(15):6440-55. PMC: 3159468. DOI: 10.1093/nar/gkr302. View

10.

Schonrock N, Ke Y, Humphreys D, Staufenbiel M, Ittner L, Preiss T . Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta. PLoS One. 2010; 5(6):e11070. PMC: 2884018. DOI: 10.1371/journal.pone.0011070. View

11.

Zhang N, Wen Q, Ren L, Liang W, Xia Y, Zhang X . Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells. Int J Mol Sci. 2013; 14(9):18657-69. PMC: 3794801. DOI: 10.3390/ijms140918657. View

12.

Ramachandran D, Roy U, Garg S, Ghosh S, Pathak S, Kolthur-Seetharam U . Sirt1 and mir-9 expression is regulated during glucose-stimulated insulin secretion in pancreatic β-islets. FEBS J. 2011; 278(7):1167-74. DOI: 10.1111/j.1742-4658.2011.08042.x. View

13.

Lu Y, Xu Y, Yin Z, Yang X, Jiang Y, Gui J . Chondrocyte migration affects tissue-engineered cartilage integration by activating the signal transduction pathways involving Src, PLCγ1, and ERK1/2. Tissue Eng Part A. 2013; 19(21-22):2506-16. DOI: 10.1089/ten.TEA.2012.0614. View

14.

Hu Y, Wen Q, Liang W, Kang T, Ren L, Zhang N . Osthole reverses beta-amyloid peptide cytotoxicity on neural cells by enhancing cyclic AMP response element-binding protein phosphorylation. Biol Pharm Bull. 2014; 36(12):1950-8. DOI: 10.1248/bpb.b13-00561. View

15.

Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva F, Li M . SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004; 6(8):731-40. DOI: 10.1038/ncb1151. View

16.

Jiang Y, Liu Y, Zhu C, Ma X, Ma L, Zhou L . Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice. Neurobiol Learn Mem. 2015; 121:20-9. DOI: 10.1016/j.nlm.2015.03.003. View

17.

Culmsee C, Monnig J, Kemp B, Mattson M . AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci. 2001; 17(1):45-58. DOI: 10.1385/JMN:17:1:45. View

18.

Malthankar-Phatak G, Lin Y, Giovannone N, Siman R . Amyloid deposition and advanced age fails to induce Alzheimer's type progression in a double knock-in mouse model. Aging Dis. 2012; 3(2):141-55. PMC: 3377826. View

19.

Ambros V . The functions of animal microRNAs. Nature. 2004; 431(7006):350-5. DOI: 10.1038/nature02871. View

20.

Kudinov A, Kudinova N, Kezlia E, Kozyrev K, Medvedev A, Berezov T . [Compensatory mechanisms to heal neuroplasticity impairment under Alzheiemer's disease neurodegeneration. I: The role of amyloid beta and its' precursor protein]. Biomed Khim. 2013; 58(4):385-99. View