Advertisement

Emerging Role of microRNAs in Cerebral Stroke Pathophysiology

  • Amit Kumar Tripathi
  • Shashi Kant Tiwari
  • Priyanka Mishra
  • Manish Jain
Chapter

Abstract

Cerebral stroke is a major cause of death and physical disability throughout the world, yet therapeutic options remain limited. The outcomes of stroke injury are critical, causing an extensive burden to both the individual patient and society. Current interventions for stroke injury have been demonstrated to be inadequate, mostly attributable to a lack of understanding of the cellular and molecular changes that occur following an ischemic cerebral stroke. MicroRNAs (miRNAs) are small, endogenous, noncoding RNA molecules that have capacity as post-transcriptional negative regulators of a target mRNA by base-pairing with the 3′- untranslated region (3′-UTR). Novel methodologies are being produced to get miRNA-related therapeutics into the brain over an intact BBB, including chemical modification, use of targeting molecules and methods of disrupting the BBB. However, circulating miRNAs are novel, stable, and potential biomarkers for the early diagnosis of acute stroke in humans. These miRNA profiles also indicate the severity of stroke results related to age and sex in rodents. In this chapter, we focus on the pathophysiological role of miRNAs as novel diagnostic and prognostic biomarkers, in addition to promising therapeutic interventions in cerebral stroke patients.

Keywords

MicroRNAs Blood–brain barrier Biomarkers Stroke Antagomir 

Abbreviations

BDNF

Brain-derived neurotrophic factor

COX2

Cyclooxygenase 2

e-NOS

Endothelial-NOS

FAP-1

Fas-associated protein-tyrosine phosphatase 1

FasL

Fas ligand

FGF2

Fibroblast growth factor 2

GAX

Growth arrest-specific homeobox

GLT-1

Glutamate transporter-1

GluR2

Glutamate receptor 2

HOXA5

Homeobox A5

HSPA12B

Heat shock protein A12B

iASPP

Inhibitory member of the apoptosis-stimulating proteins of p53 family

IGF-1

Insulin-like growth factor 1

IL

Interleukin

KIT

Kit ligand

MDA

Malondialdehyde

MMP-9

Metalloproteinases 9

MnSOD

Manganese SOD

MyD88

Myeloid differentiation primary response gene 88

NCX1

Sodium–calcium exchanger-1

NMDA

N-Methyl-D-aspartate

NPC

Neuronal progenitor cell

Nrf2

Nuclear factor erythroid-2 related factor 2

PUMA

p53 upregulated modulator of apoptosis

ROS

Reactive oxygen species

SOCS1

Suppressor of cytokine signaling 1

SOD

Superoxide dismutase

Sox9

Sry-box 9

TGF-β

Transforming growth factor-β

TLR

Toll-like receptor

TNF

Tumor necrosis factor

VEGF

Vascular endothelial growth factor

Notes

Acknowledgement

AKT gratefully acknowledges the financial support provided by the Department of Science and Technology-Science Engineering Research Board (DST-SERB) (PDF/2016/002996/LS), New Delhi, India, and the Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, for providing facilities and support.

References

  1. 1.
    Mukherjee, D., & Patil, C. G. (2011). Epidemiology and the global burden of stroke. World Neurosurgery, 76(6), S85–S90.CrossRefGoogle Scholar
  2. 2.
    Beal, C. C. (2010). Gender and stroke symptoms: A review of the current literature. Journal of Neuroscience Nursing, 42(2), 80–87.CrossRefGoogle Scholar
  3. 3.
    Liu, X., Li, F., Zhao, S., Luo, Y., Kang, J., Zhao, H., Yan, F., Li, S., & Ji, X. (2013). MicroRNA-124–mediated regulation of inhibitory member of apoptosis-stimulating protein of p53 family in experimental stroke. Stroke, 44(7), 1973–1980.CrossRefGoogle Scholar
  4. 4.
    Liu, F. J., Lim, K. Y., Kaur, P., Sepramaniam, S., Armugam, A., Wong, P. T. H., & Jeyaseelan, K. (2013). microRNAs involved in regulating spontaneous recovery in embolic stroke model. PLoS One, 8(6), e66393.CrossRefGoogle Scholar
  5. 5.
    Ouyang, Y. B., Xu, L., Lu, Y., Sun, X., Yue, S., Xiong, X. X., & Giffard, R. G. (2013). Astrocyte-enriched miR-29a targets PUMA and reduces neuronal vulnerability to forebrain ischemia. Glia, 61(11), 1784–1794.CrossRefGoogle Scholar
  6. 6.
    Yang, Z. B., Zhang, Z., Li, T. B., Lou, Z., Li, S. Y., Yang, H., Yang, J., Luo, X. J., & Peng, J. (2014). Up-regulation of brain-enriched miR-107 promotes excitatory neurotoxicity through down-regulation of glutamate transporter-1 expression following ischaemic stroke. Clinical Science, 127(12), 679–689.CrossRefGoogle Scholar
  7. 7.
    Harraz, M. M., Eacker, S. M., Wang, X., Dawson, T. M., & Dawson, V. L. (2012). MicroRNA-223 is neuroprotective by targeting glutamate receptors. Proceedings of the National Academy of Sciences, 109(46), 18962–18967.CrossRefGoogle Scholar
  8. 8.
    Zhang, L., Li, Y. J., Wu, X. Y., Hong, Z., & Wei, W. S. (2015). MicroRNA-181c negatively regulates the inflammatory response in oxygen-glucose-deprived microglia by targeting Toll-like receptor 4. Journal of Neurochemistry, 132(6), 713–723.CrossRefGoogle Scholar
  9. 9.
    Ni, J., Wang, X., Chen, S., Liu, H., Wang, Y., Xu, X., Cheng, J., Jia, J., & Zhen, X. (2015). MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain, Behavior, and Immunity, 49, 75–85.CrossRefGoogle Scholar
  10. 10.
    Vinciguerra, A., Formisano, L., Cerullo, P., Guida, N., Cuomo, O., Esposito, A., Di Renzo, G., Annunziato, L., & Pignataro, G. (2014). MicroRNA-103-1 selectively downregulates brain NCX1 and its inhibition by anti-miRNA ameliorates stroke damage and neurological deficits. Molecular Therapy, 22(10), 1829–1838.CrossRefGoogle Scholar
  11. 11.
    Chi, W., Meng, F., Li, Y., Li, P., Wang, G., Cheng, H., Han, S., & Li, J. (2014). Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B. Brain Research, 1592, 22–33.CrossRefGoogle Scholar
  12. 12.
    Wang, P., Liang, X., Lu, Y., Zhao, X., & Liang, J. (2016). MicroRNA-93 downregulation ameliorates cerebral ischemic injury through the Nrf2/HO-1 defense pathway. Neurochemical Research, 41(10), 2627–2635.CrossRefGoogle Scholar
  13. 13.
    Zhai, F., Zhang, X., Guan, Y., Yang, X., Li, Y., Song, G., & Guan, L. (2012). Expression profiles of microRNAs after focal cerebral ischemia/reperfusion injury in rats. Neural Regeneration Research, 7(12), 917.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Dharap, A., Bowen, K., Place, R., Li, L. C., & Vemuganti, R. (2009). Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. Journal of Cerebral Blood Flow & Metabolism, 29(4), 675–687.CrossRefGoogle Scholar
  15. 15.
    Schickel, R., Park, S. M., Murmann, A. E., & Peter, M. E. (2010). miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1. Molecular Cell, 38(6), 908–915.CrossRefGoogle Scholar
  16. 16.
    Wen, Y., Zhang, X., Dong, L., Zhao, J., Zhang, C., & Zhu, C. (2015). Acetylbritannilactone modulates microRNA-155-mediated inflammatory response in ischemic cerebral tissues. Molecular Medicine, 21(1), 197.CrossRefGoogle Scholar
  17. 17.
    Buller, B., Liu, X., Wang, X., Zhang, R. L., Zhang, L., Hozeska-Solgot, A., Chopp, M., & Zhang, Z. G. (2010). MicroRNA-21 protects neurons from ischemic death. The FEBS Journal, 277(20), 4299–4307.CrossRefGoogle Scholar
  18. 18.
    Tao, Z., Zhao, H., Wang, R., Liu, P., Yan, F., Zhang, C., Ji, X., & Luo, Y. (2015). Neuroprotective effect of microRNA-99a against focal cerebral ischemia-reperfusion injury in mice. Journal of the Neurological Sciences, 355(1), 113–119.CrossRefGoogle Scholar
  19. 19.
    Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W. G., van Rijen, P. C., Gorter, J. A., & Aronica, E. (2012). MicroRNA-146a: A key regulator of astrocyte-mediated inflammatory response. PLoS One, 7(9), e44789.CrossRefGoogle Scholar
  20. 20.
    Yin, K. J., Deng, Z., Huang, H., Hamblin, M., Xie, C., Zhang, J., & Chen, Y. E. (2010). miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiology of Disease, 38(1), 17–26.CrossRefGoogle Scholar
  21. 21.
    Suárez, Y., Fernández-Hernando, C., Pober, J. S., & Sessa, W. C. (2007). Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circulation Research, 100(8), 1164–1173.CrossRefGoogle Scholar
  22. 22.
    Zhao, H., Wang, J., Gao, L., Wang, R., Liu, X., Gao, Z., Tao, Z., Xu, C., Song, J., Ji, X., & Luo, Y. (2013). MiRNA-424 protects against permanent focal cerebral ischemia injury in mice involving suppressing microglia activation. Stroke, 44(6), 1706–1713.CrossRefGoogle Scholar
  23. 23.
    Banerjee, S., Xie, N., Cui, H., Tan, Z., Yang, S., Icyuz, M., Abraham, E., & Liu, G. (2013). MicroRNA let-7c regulates macrophage polarization. The Journal of Immunology, 190(12), 6542–6549.CrossRefGoogle Scholar
  24. 24.
    Hua, Z., Lv, Q., Ye, W., Wong, C. K. A., Cai, G., Gu, D., Ji, Y., Zhao, C., Wang, J., Yang, B. B., & Zhang, Y. (2006). MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One, 1(1), e116.CrossRefGoogle Scholar
  25. 25.
    Xie, W., Li, M., Xu, N., Lv, Q., Huang, N., He, J., & Zhang, Y. (2013). MiR-181a regulates inflammation responses in monocytes and macrophages. PLoS One, 8(3), e58639.CrossRefGoogle Scholar
  26. 26.
    Yan, W., Zhang, W., Sun, L., Liu, Y., You, G., Wang, Y., Kang, C., You, Y., & Jiang, T. (2011). Identification of MMP-9 specific microRNA expression profile as potential targets of anti-invasion therapy in glioblastoma multiforme. Brain Research, 1411, 108–115.CrossRefGoogle Scholar
  27. 27.
    Zhang, J. F., Shi, L. L., Zhang, L., Zhao, Z. H., Liang, F., Xu, X., Zhao, L. Y., Yang, P. B., Zhang, J. S., & Tian, Y. F. (2016). MicroRNA-25 negatively regulates cerebral ischemia/reperfusion injury-induced cell apoptosis through Fas/FasL pathway. Journal of Molecular Neuroscience, 58(4), 507–516.CrossRefGoogle Scholar
  28. 28.
    Wei, N., Xiao, L., Xue, R., Zhang, D., Zhou, J., Ren, H., Guo, S., & Xu, J. (2016). MicroRNA-9 mediates the cell apoptosis by targeting Bcl2l11 in ischemic stroke. Molecular Neurobiology, 53(10), 6809–6817.CrossRefGoogle Scholar
  29. 29.
    Huang, W., Liu, X., Cao, J., Meng, F., Li, M., Chen, B., & Zhang, J. (2015). miR-134 regulates ischemia/reperfusion injury-induced neuronal cell death by regulating CREB signaling. Journal of Molecular Neuroscience, 55(4), 821–829.CrossRefGoogle Scholar
  30. 30.
    Liu, P., Zhao, H., Wang, R., Wang, P., Tao, Z., Gao, L., Yan, F., Liu, X., Yu, S., Ji, X., & Luo, Y. (2014). MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress. Stroke, 9, e91661.Google Scholar
  31. 31.
    Moon, J. M., Xu, L., & Giffard, R. G. (2013). Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss. Journal of Cerebral Blood Flow & Metabolism, 33(12), 1976–1982.CrossRefGoogle Scholar
  32. 32.
    Selvamani, A., Sathyan, P., Miranda, R. C., & Sohrabji, F. (2012). An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS One, 7(2), e32662.CrossRefGoogle Scholar
  33. 33.
    Cheng, L. C., Pastrana, E., Tavazoie, M., & Doetsch, F. (2009). miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nature Neuroscience, 12(4), 399–408.CrossRefGoogle Scholar
  34. 34.
    Xu, L. J., Ouyang, Y. B., Xiong, X., Stary, C. M., & Giffard, R. G. (2015). Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia. Experimental Neurology, 264, 1–7.CrossRefGoogle Scholar
  35. 35.
    Edbauer, D., Neilson, J. R., Foster, K. A., Wang, C. F., Seeburg, D. P., Batterton, M. N., Tada, T., Dolan, B. M., Sharp, P. A., & Sheng, M. (2010). Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron, 65(3), 373–384.Google Scholar
  36. 36.
    Mellios, N., Huang, H. S., Grigorenko, A., Rogaev, E., & Akbarian, S. (2008). A set of differentially expressed miRNAs, including miR-30a-5p, act as post-transcriptional inhibitors of BDNF in prefrontal cortex. Human Molecular Genetics, 17(19), 3030–3042.CrossRefGoogle Scholar
  37. 37.
    Yin, K. J., Olsen, K., Hamblin, M., Zhang, J., Schwendeman, S. P., & Chen, Y. E. (2012). Vascular endothelial cell-specific microRNA-15a inhibits angiogenesis in hindlimb ischemia. Journal of Biological Chemistry, 287(32), 27055–27064.CrossRefGoogle Scholar
  38. 38.
    Chen, Y., & Gorski, D. H. (2008). Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood, 111(3), 1217–1226.CrossRefGoogle Scholar
  39. 39.
    Sepramaniam, S., Armugam, A., Lim, K. Y., Karolina, D. S., Swaminathan, P., Tan, J. R., & Jeyaseelan, K. (2010). MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. Journal of Biological Chemistry, 285(38), 29223–29230.CrossRefGoogle Scholar
  40. 40.
    Jickling, G. C., & Sharp, F. R. (2015). Biomarker panels in ischemic stroke. Stroke, 46(3), 915–920.CrossRefGoogle Scholar
  41. 41.
    Sepramaniam, S., Tan, J. R., Tan, K. S., DeSilva, D. A., Tavintharan, S., Woon, F. P., Wang, C. W., Yong, F. L., Karolina, D. S., Kaur, P., & Liu, F. J. (2014). Circulating microRNAs as biomarkers of acute stroke. International Journal of Molecular Sciences, 15(1), 1418–1432.CrossRefGoogle Scholar
  42. 42.
    Onwuekwe, I. O., & Ezeala-Adikaibe, B. (2012). Ischemic stroke and neuroprotection. Annals of Medical and Health Sciences Research, 2(2), 186–190.CrossRefGoogle Scholar
  43. 43.
    Guyot, L. L., Diaz, F. G., O’Regan, M. H., McLeod, S., Park, H., & Phillis, J. W. (2001). Real-time measurement of glutamate release from the ischemic penumbra of the rat cerebral cortex using a focal middle cerebral artery occlusion model. Neuroscience Letters, 299(1), 37–40.CrossRefGoogle Scholar
  44. 44.
    Ohta, K., Graf, R., Rosner, G., & Heiss, W. D. (2001). Calcium ion transients in peri-infarct depolarizations may deteriorate ion homeostasis and expand infarction in focal cerebral ischemia in cats. Stroke, 32(2), 535–543.CrossRefGoogle Scholar
  45. 45.
    Annunziato, L., Pignataro, G., & Di Renzo, G. F. (2004). Pharmacology of brain Na+/Ca2+ exchanger: From molecular biology to therapeutic perspectives. Pharmacological Reviews, 56(4), 633–654.CrossRefGoogle Scholar
  46. 46.
    Boscia, F., Gala, R., Pignataro, G., De Bartolomeis, A., Cicale, M., Ambesi-Impiombato, A., Di Renzo, G., & Annunziato, L. (2006). Permanent focal brain ischemia induces isoform-dependent changes in the pattern of Na+/Ca2+ exchanger gene expression in the ischemic core, periinfarct area, and intact brain regions. Journal of Cerebral Blood Flow & Metabolism, 26(4), 502–517.CrossRefGoogle Scholar
  47. 47.
    Tortiglione, A., Pignataro, G., Minale, M., Secondo, A., Scorziello, A., Di Renzo, G. F., Amoroso, S., Caliendo, G., Santagada, V., & Annunziato, L. (2002). Na+/Ca2+ exchanger in Na+ efflux-Ca2+ influx mode of operation exerts a neuroprotective role in cellular models of in vitro anoxia and in vivo cerebral ischemia. Annals of the New York Academy of Sciences, 976(1), 408–412.CrossRefGoogle Scholar
  48. 48.
    Jickling, G. C., & Sharp, F. R. (2011). Blood biomarkers of ischemic stroke. Neurotherapeutics, 8(3), 349.CrossRefGoogle Scholar
  49. 49.
    Zhan, X., Jickling, G. C., Tian, Y., Stamova, B., Xu, H., Ander, B. P., Turner, R. J., Mesias, M., Verro, P., Bushnell, C., & Johnston, S. C. (2011). Transient ischemic attacks characterized by RNA profiles in blood. Neurology, 77(19), 1718–1724.CrossRefGoogle Scholar
  50. 50.
    Hacke, W., Kaste, M., Fieschi, C., von Kummer, R., Davalos, A., Meier, D., Larrue, V., Bluhmki, E., Davis, S., Donnan, G., & Schneider, D. (1998). Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). The Lancet, 352(9136), 1245–1251.Google Scholar
  51. 51.
    Albers, G. W., Bates, V. E., Clark, W. M., Bell, R., Verro, P., & Hamilton, S. A. (2000). Intravenous tissue-type plasminogen activator for treatment of acute stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA, 283(9), 1145–1150.CrossRefGoogle Scholar
  52. 52.
    Wahlgren, N., Ahmed, N., Dávalos, A., Ford, G. A., Grond, M., Hacke, W., Hennerici, M. G., Kaste, M., Kuelkens, S., Larrue, V., & Lees, K. R. (2007). Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): An observational study. The Lancet, 369(9558), 275–282.Google Scholar
  53. 53.
    Kuebler, P., & Genentech, Inc., 2007. Method of treating stroke with thrombolytic agent. U.S. Patent Application 11/832,291.Google Scholar
  54. 54.
    Son, S., Jang, J., Youn, H., Lee, S., Lee, D., Lee, Y. S., Jeong, J. M., Kim, W. J., & Lee, D. S. (2011). A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials, 32(21), 4968–4975.CrossRefGoogle Scholar
  55. 55.
    Pardridge, W. M. (2004). Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opinion on Biological Therapy, 4(7), 1103–1113.CrossRefGoogle Scholar
  56. 56.
    Pardridge, W. M. (2007). shRNA and siRNA delivery to the brain. Advanced Drug Delivery Reviews, 59(2), 141–152.CrossRefGoogle Scholar
  57. 57.
    Ruberti, F., Barbato, C., & Cogoni, C. (2012). Targeting microRNAs in neurons: Tools and perspectives. Experimental Neurology, 235(2), 419–426.CrossRefGoogle Scholar
  58. 58.
    Liu, X. S., Chopp, M., Zhang, R. L., Tao, T., Wang, X. L., Kassis, H., Hozeska-Solgot, A., Zhang, L., Chen, C., & Zhang, Z. G. (2011). MicroRNA profiling in subventricular zone after stroke: MiR-124a regulates proliferation of neural progenitor cells through Notch signaling pathway. PLoS One, 6(8), e23461.CrossRefGoogle Scholar
  59. 59.
    Bouchie, A. (2013). First microRNA mimic enters clinic. Nature Biotechnology, 31, 577.CrossRefGoogle Scholar
  60. 60.
    Leclercq, M., Diallo, A. B., & Blanchette, M. (2017). Prediction of human miRNA target genes using computationally reconstructed ancestral mammalian sequences. Nucleic Acids Research, 45(2), 556–566.CrossRefGoogle Scholar
  61. 61.
    Ouyang, Y. B., Lu, Y., Yue, S., Xu, L. J., Xiong, X. X., White, R. E., Sun, X., & Giffard, R. G. (2012). miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. Neurobiology of Disease, 45(1), 555–563.Google Scholar
  62. 62.
    Zhu, F., Liu, J. L., Li, J. P., Xiao, F., Zhang, Z. X., & Zhang, L. (2014). MicroRNA-124 (miR-124) regulates Ku70 expression and is correlated with neuronal death induced by ischemia/ reperfusion. Journal of Molecular Neuroscience, 52(1), 148–155.Google Scholar
  63. 63.
    Ouyang, Y. B., Lu, Y., Yue, S., & Giffard, R. G. (2012). miR-181 targets multiple Bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes. Mitochondrion, 12(2), 213–219.Google Scholar
  64. 64.
    Yin, K. J., Hamblin, M., & Eugene Chen, Y. (2015). Angiogenesis-regulating microRNAs and ischemic stroke. Current Vascular Pharmacology, 13(3), 352–365.Google Scholar
  65. 65.
    Bhalala, O. G., Srikanth, M., & Kessler, J. A. (2013). The emerging roles of microRNAs in CNS injuries. Nature Reviews Neurology, 9(6), 328–339.Google Scholar
  66. 66.
    Allen, C. L., & Bayraktutan, U. (2009). Oxidative stress and its role in the pathogenesis of ischaemic stroke. International Journal of Stroke, 4(6), 461–470.CrossRefGoogle Scholar
  67. 67.
    Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., Marzluff, W. F., & Sharpless, N. E. (2013). Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA, 19(2), 141–157.CrossRefGoogle Scholar
  68. 68.
    Lu, D., & Xu, A. D. (2016). Mini review: Circular RNAs as potential clinical biomarkers for disorders in the central nervous system. Frontiers in Genetics, 7, 53.CrossRefGoogle Scholar
  69. 69.
    Han, B., Zhang, Y., Zhang, Y., Bai, Y., Chen, X., Huang, R., Wu, F., Leng, S., Chao, J., Zhang, J. H., & Hu, G. (2018). Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: Implications for cerebral ischemic stroke. Autophagy, 14(7), 1164–1184.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Amit Kumar Tripathi
    • 1
  • Shashi Kant Tiwari
    • 2
  • Priyanka Mishra
    • 3
  • Manish Jain
    • 4
  1. 1.School of Biomedical EngineeringIndian Institute of Technology (Banaras Hindu University)VaranasiIndia
  2. 2.Department of PediatricsUniversity of CaliforniaSan DiegoUSA
  3. 3.Department of NeurosciencesUniversity of CaliforniaSan DiegoUSA
  4. 4.Department of Internal MedicineUniversity of IowaIowa CityUSA

Personalised recommendations