The Protective Role of MicroRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2016 Dec 24

PMID 28008308

Citations 30

Authors

Qi Wu

Xiaoyang Ye

Yi Xiong

Haili Zhu

Jianting Miao

Wei Zhang

Jun Wan

Affiliations

Soon will be listed here.

Abstract

MicroRNAs are small non-coding RNAs that repress the expression of their target proteins. The roles of microRNAs in the development of Alzheimer's disease (AD) are not clear. In this study we show that miR-200c represses the expression of PTEN protein. PTEN downregulation by miR-200c supports the survival and differentiation of cultured neurons. AD is a progressive neurodegenerative disease signified by beta amyloid (Aβ) peptide aggregation and deposition. In a mouse model of AD that is induced by and Δ double transgenes, we found Aβ deposition results in neuronal ER stress that induces miR200c. Pharmacological blockade of ER stress inhibited Aβ-induced miR-200c overexpression in AD brains. MiR-200c was detected in the serum of both AD mice and human AD patients. These findings suggest that miR-200c functions as part of the neuronal cell-intrinsic adaptive machinery, and supports neuronal survival and differentiation in response to Aβ induced ER-stress by downregulating PTEN.

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References

Querfurth H, LaFerla F . Alzheimer's disease. N Engl J Med. 2010; 362(4):329-44. DOI: 10.1056/NEJMra0909142. View

Jurgensen S, Ferreira S . Nicotinic receptors, amyloid-beta, and synaptic failure in Alzheimer's disease. J Mol Neurosci. 2009; 40(1-2):221-9. DOI: 10.1007/s12031-009-9237-0. View

Rattray M . Is there nicotinic modulation of nerve growth factor? Implications for cholinergic therapies in Alzheimer's disease. Biol Psychiatry. 2001; 49(3):185-93. DOI: 10.1016/s0006-3223(00)01047-7. View

Logue S, Cleary P, Saveljeva S, Samali A . New directions in ER stress-induced cell death. Apoptosis. 2013; 18(5):537-46. DOI: 10.1007/s10495-013-0818-6. View

Choi P, Zakhary L, Choi W, Caron S, Alvarez-Saavedra E, Miska E . Members of the miRNA-200 family regulate olfactory neurogenesis. Neuron. 2008; 57(1):41-55. PMC: 2204047. DOI: 10.1016/j.neuron.2007.11.018. View

Yang F, Zhang L, Wang F, Wang Y, Huo X, Yin Y . Modulation of the unfolded protein response is the core of microRNA-122-involved sensitivity to chemotherapy in hepatocellular carcinoma. Neoplasia. 2011; 13(7):590-600. PMC: 3132845. DOI: 10.1593/neo.11422. View

Groenendyk J, Fan X, Peng Z, Ilnytskyy Y, Kurgan L, Michalak M . Genome-wide analysis of thapsigargin-induced microRNAs and their targets in NIH3T3 cells. Genom Data. 2015; 2:325-7. PMC: 4535834. DOI: 10.1016/j.gdata.2014.10.002. View

Cornejo V, Hetz C . The unfolded protein response in Alzheimer's disease. Semin Immunopathol. 2013; 35(3):277-92. DOI: 10.1007/s00281-013-0373-9. View

Pandey A, Singh P, Jauhari A, Singh T, Khan F, Pant A . Critical role of the miR-200 family in regulating differentiation and proliferation of neurons. J Neurochem. 2015; 133(5):640-52. DOI: 10.1111/jnc.13089. View

10.

Vilardo E, Barbato C, Ciotti M, Cogoni C, Ruberti F . MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons. J Biol Chem. 2010; 285(24):18344-51. PMC: 2881760. DOI: 10.1074/jbc.M110.112664. View

11.

Musatov S, Roberts J, Brooks A, Pena J, Betchen S, Pfaff D . Inhibition of neuronal phenotype by PTEN in PC12 cells. Proc Natl Acad Sci U S A. 2004; 101(10):3627-31. PMC: 373513. DOI: 10.1073/pnas.0308289101. View

12.

Borchelt D, Davis J, Fischer M, Lee M, Slunt H, Ratovitsky T . A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal. 1996; 13(6):159-63. DOI: 10.1016/s1050-3862(96)00167-2. View

13.

Fonseca A, Ferreiro E, Oliveira C, Cardoso S, Pereira C . Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells. Biochim Biophys Acta. 2013; 1832(12):2191-203. DOI: 10.1016/j.bbadis.2013.08.007. View

14.

Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H . MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease. EMBO J. 2014; 33(15):1667-80. PMC: 4194100. DOI: 10.15252/embj.201387576. View

15.

Malhi H . MICRORNAs IN ER STRESS: DIVERGENT ROLES IN CELL FATE DECISIONS. Curr Pathobiol Rep. 2014; 2(3):117-122. PMC: 4235760. DOI: 10.1007/s40139-014-0046-y. View

16.

Li B, Sun H . MiR-26a promotes neurite outgrowth by repressing PTEN expression. Mol Med Rep. 2013; 8(2):676-80. DOI: 10.3892/mmr.2013.1534. View

17.

Urra H, Dufey E, Lisbona F, Rojas-Rivera D, Hetz C . When ER stress reaches a dead end. Biochim Biophys Acta. 2013; 1833(12):3507-3517. DOI: 10.1016/j.bbamcr.2013.07.024. View

18.

Polito V, Li H, Martini-Stoica H, Wang B, Yang L, Xu Y . Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med. 2014; 6(9):1142-60. PMC: 4197862. DOI: 10.15252/emmm.201303671. View

19.

Zhou J, Parada L . PTEN signaling in autism spectrum disorders. Curr Opin Neurobiol. 2012; 22(5):873-9. DOI: 10.1016/j.conb.2012.05.004. View

20.

Knafo S, Sanchez-Puelles C, Palomer E, Delgado I, Draffin J, Mingo J . PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Nat Neurosci. 2016; 19(3):443-53. DOI: 10.1038/nn.4225. View