MicroRNA-based Therapeutics in Central Nervous System Injuries

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2018 May 1

PMID 29708005

Citations 115

Authors

Ping Sun

Da Zhi Liu

Glen C Jickling

Frank R Sharp

Ke-Jie Yin

Affiliations

Soon will be listed here.

Abstract

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.

Citing Articles

The miR-451a facilitates natural killer cell-associated immune deficiency after ischemic stroke.

Li Y, Guan X, Lan T, Zhang Z, Zhang Y, Jiang S J Cereb Blood Flow Metab. 2025; :271678X251321641.

PMID: 39985210 PMC: 11846095. DOI: 10.1177/0271678X251321641.

The Application of MicroRNAs in Traumatic Brain Injury: Mechanism Elucidation and Clinical Translation.

Wang H, Fan X, Zhang Y, Ma N, Li L, Lu Q Mol Neurobiol. 2025; .

PMID: 39946001 DOI: 10.1007/s12035-025-04737-4.

Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles.

Chen S, Dou Y, Zhang Y, Sun X, Liu X, Yang Q J Orthop Translat. 2025; 50:44-55.

PMID: 39868351 PMC: 11761297. DOI: 10.1016/j.jot.2024.09.014.

Preliminary Evidence for Neuronal Dysfunction Following Adverse Childhood Experiences: An Investigation of Salivary MicroRNA Within a High-Risk Youth Sample.

Schmidt A, Hicks S, Bergquist B, Maloney K, Dennis V, Bammel A Genes (Basel). 2024; 15(11).

PMID: 39596633 PMC: 11593590. DOI: 10.3390/genes15111433.

The neuroinflammatory role of microRNAs in Alzheimer's disease: pathological insights to therapeutic potential.

Liu W, Rao X, Sun W, Chen X, Yu L, Zhang J Mol Cell Biochem. 2024; .

PMID: 39567427 DOI: 10.1007/s11010-024-05164-0.

References

Shi X, Yan C, Liu B, Yang C, Nie X, Wang X . miR-381 Regulates Neural Stem Cell Proliferation and Differentiation via Regulating Hes1 Expression. PLoS One. 2015; 10(10):e0138973. PMC: 4591969. DOI: 10.1371/journal.pone.0138973. View

Hu J, Huang J, Zeng L, Wang G, Cao M, Lu H . Anti-apoptotic effect of microRNA-21 after contusion spinal cord injury in rats. J Neurotrauma. 2013; 30(15):1349-60. PMC: 3727528. DOI: 10.1089/neu.2012.2748. View

Huang J, Cao Y, Zeng L, Wang G, Cao M, Lu H . Tetramethylpyrazine enhances functional recovery after contusion spinal cord injury by modulation of MicroRNA-21, FasL, PDCD4 and PTEN expression. Brain Res. 2016; 1648(Pt A):35-45. DOI: 10.1016/j.brainres.2016.07.023. View

Liu K, Yan L, Jiang X, Yu Y, Liu H, Gu T . Acquired inhibition of microRNA-124 protects against spinal cord ischemia-reperfusion injury partially through a mitophagy-dependent pathway. J Thorac Cardiovasc Surg. 2017; 154(5):1498-1508. DOI: 10.1016/j.jtcvs.2017.05.046. View

Mandic L, Traxler D, Gugerell A, Zlabinger K, Lukovic D, Pavo N . Molecular Imaging of Angiogenesis in Cardiac Regeneration. Curr Cardiovasc Imaging Rep. 2016; 9(10):27. PMC: 5018257. DOI: 10.1007/s12410-016-9389-6. View

Cordeiro M, Horn A . Stem cell therapy in intracerebral hemorrhage rat model. World J Stem Cells. 2015; 7(3):618-29. PMC: 4404396. DOI: 10.4252/wjsc.v7.i3.618. View

Zeng L, Liu J, Wang Y, Wang L, Weng S, Tang Y . MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia. Front Biosci (Elite Ed). 2011; 3(4):1265-72. DOI: 10.2741/e330. View

Bang O, Kim E, Cha J, Moon G . Adult Stem Cell Therapy for Stroke: Challenges and Progress. J Stroke. 2016; 18(3):256-266. PMC: 5066440. DOI: 10.5853/jos.2016.01263. View

Sun L, Liu A, Zhang J, Ji W, Li Y, Yang X . miR-23b improves cognitive impairments in traumatic brain injury by targeting ATG12-mediated neuronal autophagy. Behav Brain Res. 2016; 340:126-136. DOI: 10.1016/j.bbr.2016.09.020. View

10.

Ujigo S, Kamei N, Hadoush H, Fujioka Y, Miyaki S, Nakasa T . Administration of microRNA-210 promotes spinal cord regeneration in mice. Spine (Phila Pa 1976). 2014; 39(14):1099-107. DOI: 10.1097/BRS.0000000000000356. View

11.

Yin K, Deng Z, Huang H, Hamblin M, Xie C, Zhang J . miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol Dis. 2010; 38(1):17-26. PMC: 2837803. DOI: 10.1016/j.nbd.2009.12.021. View

12.

Hicks S, Johnson J, Carney M, Bramley H, Olympia R, Loeffert A . Overlapping MicroRNA Expression in Saliva and Cerebrospinal Fluid Accurately Identifies Pediatric Traumatic Brain Injury. J Neurotrauma. 2017; 35(1):64-72. PMC: 7227420. DOI: 10.1089/neu.2017.5111. View

13.

Scherrer N, Fays F, Mueller B, Luft A, Fluri F, Christ-Crain M . MicroRNA 150-5p Improves Risk Classification for Mortality within 90 Days after Acute Ischemic Stroke. J Stroke. 2017; 19(3):323-332. PMC: 5647633. DOI: 10.5853/jos.2017.00423. View

14.

Gahan P, Swaminathan R . Circulating nucleic acids in plasma and serum. Recent developments. Ann N Y Acad Sci. 2008; 1137:1-6. DOI: 10.1196/annals.1448.050. View

15.

Ganesan J, Ramanujam D, Sassi Y, Ahles A, Jentzsch C, Werfel S . MiR-378 controls cardiac hypertrophy by combined repression of mitogen-activated protein kinase pathway factors. Circulation. 2013; 127(21):2097-106. DOI: 10.1161/CIRCULATIONAHA.112.000882. View

16.

Zhu J, Zhou L, XingWu F . Tracking neural stem cells in patients with brain trauma. N Engl J Med. 2006; 355(22):2376-8. DOI: 10.1056/NEJMc055304. View

17.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

18.

Sabirzhanov B, Zhao Z, Stoica B, Loane D, Wu J, Borroto C . Downregulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of proapoptotic Bcl-2 proteins. J Neurosci. 2014; 34(30):10055-71. PMC: 4107397. DOI: 10.1523/JNEUROSCI.1260-14.2014. View

19.

Van Rooij E, Purcell A, Levin A . Developing microRNA therapeutics. Circ Res. 2012; 110(3):496-507. DOI: 10.1161/CIRCRESAHA.111.247916. View

20.

Garzon R, Marcucci G, Croce C . Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010; 9(10):775-89. PMC: 3904431. DOI: 10.1038/nrd3179. View