Article Figures & Data
Figures
- Fig. 1.
Common neurosystemic diseases and lncRNAs associated with neuroinflammation. Some common neurosystemic diseases include ischemic stroke, Alzheimer's disease, Parkinson's disease, traumatic brain injury, epilepsy, multiple sclerosis, spinal cord ischemia, neuropathic pain, and multiple sclerosis. Each disease has its own unique pathologic features, but neuroinflammation is the common pathologic process. Reducing the production of neuroinflammation in a way that improves the brain environment, protects nerve cells, and alleviates the progression of the disease. Accumulated studies have confirmed that lncRNAs play pro-inflammatory or anti-inflammatory roles in the regulation of neuroinflammation. Furthermore, lncRNAs including MALAT1, NEAT1, TUG1, SNHG family, H19, MEG3, XIST, GAS5, UCA1, and GM4419 have been found to alleviate more than one neurosystemic disease by regulating neuroinflammation.
- Fig. 2.
CeRNA networks in neuroinflammation. Among the mechanisms by which lncRNAs regulate neuroinflammation, the ceRNA network has been studied more widely. CeRNA network consists of lncRNA, miRNA, and mRNA. Specifically, lncRNA targets the 3′-UTR of miRNA to regulate downstream mRNA.
- Fig. 3.
Signal pathways in neuroinflammation. Neuroinflammation-related signaling pathways include NFκB, Notch, PI3K/AKT, and so on. NFκB is the main pathway of lncRNAs to regulate neuroinflammation.
Tables
- TABLE 1
Functional characterizations of lncRNAs in neuroinflammation-related diseases.
Expression of 10 lncRNAs (MALAT1, NEAT1, TUG1, SNHG family, H19, MEG3, XIST, GAS5, UCA1, and GM4419) in different neurosystemic disease (ischemic stroke, Alzheimer's disease, Parkinson's disease, traumatic brain injury, epilepsy, multiple sclerosis, spinal cord ischemia, neuropathic pain, and multiple sclerosis) models and biologic functions of lncRNAs by regulating downstream targets.
LncRNA Disease Model Expression Role Downstream Functional role Reference MALAT1 Alzheimer’s disease Cell model: PC12 cells are terated with NGF;
animal model: SD rats are injected with Aβ1-42Down Anti-inflammatory miR-125b/PTGS2,CDK5, FOXQ1 Inhibiting neuron apoptosis and neuroinflammation; stimulating neurite outgrowth Ma et al., 2019 Parkinson’s disease Cell model: BV2 and N2a cells are treated with LPS;
animal model: C57BL/6 mice are injected with MPTP-hydrochlorideUp Pro-inflammatory EZH2-NRF2 Promoting inflammasome activation and reactive oxygen species production; shortening the movement time Cai et al., 2020b Traumatic brain injury Animal model: male rats' brains are impacted at the frontoparietal cortex reaching a depth of 0.5 mm below the dura matter layer Up
(by hASC-derived exosomes)Anti-inflammatory The microRNAs and the small nucleolar RNAs Recovering motor behavior function; reducing cortical brain injury Patel et al., 2018 Acute spinal cord injury Animal model: a 10g weight drop from a 2.5-cm height on a T10 spinal cord of the SD rat Up Pro-inflammatory miR-199b/ IKKβ/ NF-κB Promoting microglia activation and neuroinflammation; destroying the hindlimb locomotor activity Zhou et al., 2018a Ischemic stroke Cell model: rBMVEC cells are placed in an oxygen and glucose deprivation condition and reperfusion;
animal model: SD rats are subjected to transient middle cerebral artery occlusionUp (by polydatin) Anti-inflammatory C/EBPβ/MALAT1/CREB/PGC-1α/PPARγ Protecting brain microvascular integrity and ameliorating stroke Ruan et al., 2019 Multiple sclerosis Cell model: primary macrophages and splenocytes are treated with LPS;
animal model: C57BL/6 mice are injected with MOG35–55/CFADown Anti-inflammatory None Promoting the pattern of macrophage and T cell differentiation toward anti-inflammatory phenotype Masoumi et al., 2019 Neuropathic pain Animal model: the bilateral sciatic nerves of SD rats are ligated Up Pro-inflammatory miR-129-5p/HMGB1 Promoting the development of neuropathic pain and neuroinflammation Ma et al., 2020b Neuropathic pain Animal model: the bilateral sciatic nerves of SD rats are ligated Up Pro-inflammatory miR-206/ZEB2 Promoting the development of neuropathic pain and neuroinflammation Chen et al., 2019b Neuropathic pain Animal model: the bilateral sciatic nerves of SD rats are ligated Up Pro-inflammatory miR-154-5p/AQp9 Promoting the development of neuropathic pain and neuroinflammation Wu et al., 2020b NEAT1 Parkinson’s disease Cell model: SK-N-SH cells are treated with MPP+;
animal model: C57BL/6 mice are injected with MPTPUp Pro-inflammatory miR-212-3p/AX1N1 Promoting apoptosis and inflammation; inhibiting cell viability Liu et al., 2021d Parkinson’s disease Cell model: SK-N-SH cells are treated with MPP+ Up Pro-inflammatory miR-212-5p/RAB3IP Promoting apoptosis and inflammation Liu et al., 2020c Neuropathic pain Animal model: the bilateral sciatic nerves of SD rats are ligated Up Pro-inflammatory miR-381/HMGB1 Promoting the development of neuropathic pain and neuroinflammation Xia et al., 2018 Epilepsy Cell model: CTX-TNA cells are treated with IL-1β Up Pro-inflammatory miR-129-5p/Notch Promoting inflammation; inhibiting cell viability Wan and Yang, 2020 Ischemic stroke Cell model: microglia cells are placed in an oxygen and glucose deprivation condition and reperfusion Up
(by YY1)Pro-inflammatory YY1/NEAT1/Wnt/β-catenin Promoting inflammation and apoptosis of microglial cells Han and Zhou, 2019 Traumatic brain injury Animal model: C57BL/6 mice' brains are impacted at the frontoparietal cortex reaching a depth of 0.5 mm below the dura matter layer Up
(by bexarotene)Anti-inflammatory Bexarotene/RXR-α/ NEAT1/PIDD1 Inhibiting apoptosis and inflammation Zhong et al., 2017 Cerebral ischemic reperfusion Cell model: BV2 cells are placed in an oxygen and glucose deprivation condition and reperfusion Up Anti-inflammatory AKT/STAT3 Promoting cell viability; inhibiting microglial M1 polarization and cell apoptosis Ni et al., 2020 TUG1 Parkinson’s disease Cell model: BV2 cells are treated with LPS;
animal model: C57/BL mice are injected with MPTPUp Pro-inflammatory None Promoting inflammation of BV2 cell and inhibiting motor coordination ability of PD mice Cheng et al., 2021 Parkinson’s disease Cell model: SH-SY5Y cells are treated with MPP+;
animal model: C57BL/6 mice are injected with MPTPUp Pro-inflammatory miR-152-3p/PTEN Promoting apoptosis and inflammation and oxidative stress Zhai et al., 2020 Multiple sclerosis Cell model: BV2 cells are treated with LPS;
animal model: C57BL/6 mice are injected with MOG35–55Up Pro-inflammatory miR-9-5p/NF-κB1 Promoting inflammation Yue et al., 2019 Ischemic stroke Cell model: BV2 cells are placed in an oxygen and glucose deprivation condition and reperfusion Up Pro-inflammatory miR-145a-5p/NF-κB Promoting microglial M1 polarization and neuroinflammation Wang et al., 2019a Spinal cord ischemia reperfusion Animal model: the descending aorta is cross-clamped distal to the left subclavian artery of the SD rat for 14 minutes; the clamp is removed and reperfusion is continued Up Pro-inflammatory miR-29b-1-5p/MTDH/ NF-κB/IL-1β Promoting inflammation damage (neurologic defects and blood-spinal cord barrier leakage) Jia et al., 2021 Spinal cord ischemia reperfusion Animal model: the descending aorta is cross-clamped distal to the left subclavian artery of the SD rat for 14 minutes; the clamp is removed and reperfusion is continued. Up Pro-inflammatory TRIL/TLR4/NF-κB/IL-1β Promoting microglial activation and inflammation damage (neurologic deficit and blood-spinal cord barrier leakage) Jia et al., 2019 SNHG family Ischemic stroke Cell model: HCMEC/D3 cells are placed in an oxygen and glucose deprivation condition and reperfusion Down Anti-inflammatory miR-376a/CBS/H2S Inhibiting apoptosis and inflammation Lv et al., 2021b Parkinson’s disease Cell model: BV2 cells are treated with LPS;
animal model: C57BL/6 mice are injected with MPTP-HCLUp Pro-inflammatory miR-7/NLRP3 Promoting microglial activation and inflammation; promoting primary dopaminergic neurons apoptosis Cao et al., 2018 Neuropathic pain Animal model: the fifth lumbar spinal nerve of the SD rat is isolated and ligated using 6-0 silk suture Up Pro-inflammatory CDK4 Promoting neuroinflammation and neuropathic pain progression Zhang et al., 2020b Neuropathic pain Animal model: the fifth lumbar spinal nerve of SD rat is isolated and ligated using 6-0 silk suture Up Pro-inflammatory miR-423-5p Promoting neuroinflammation and neuropathic pain progression Pan et al., 2020 Ischemic stroke Cell model: primary microglial cells are placed in an oxygen and glucose deprivation condition and reperfusion;
animal model: SD rats are subjected to transient middle cerebral artery occlusion and reperfusionDown Anti-inflammatory miR-425-5p/SIRT1/NF-κB Inhibiting microglial inflammation and BMECs injury Tian et al., 2021 Ischemic stroke Cell model: BV2 cells are placed in an oxygen and glucose deprivation condition and reperfusion;
animal model: C57BL/6 mice are subjected to transient middle cerebral artery occlusion and reperfusionUp Pro-inflammatory miR-199b/AQP4 Promoting inflammation and oxidative stress of BV2; inhibiting cell viability Zhang et al., 2021b Ischemic stroke Cell model: PC12 cells are placed in an oxygen and glucose deprivation condition and reperfusion Up Pro-inflammatory miR-455-3p/TP53INP1 Promoting inflammation, apoptosis, and oxidative stress of PC12; inhibiting cell viability Fan et al., 2021 H19 Spinal cord injury Cell model: BV2 cells are treated with LPS;
animal model: the dural sac of BALB/c mice is combatedUp Pro-inflammatory miR-325-3p/NEUROD4 Up apoptosis and inflammation of BV2 cells Gu et al., 2021 Temporal lobe epilepsy Animal model: the intra-amygdala of the SD rat is injected with KA Up Pro-inflammatory JAK/STAT Promoting activation of astrocytes and microglia and inflammation Han et al., 2018 Ischemic stroke Cell model: BV2 cells are placed in an oxygen and glucose deprivation condition and reperfusion;
animal model: C57BL/6 mice are subjected to transient middle cerebral artery occlusion and reperfusionUp Pro-inflammatory HDAC1 Promoting M1 microglial polarization and inflammation Wang et al., 2017a MEG3 Cerebral ischemia reperfusion Cell model: SK-N-SH and SH-SY5Y cells are placed in an oxygen and glucose deprivation condition and reperfusion;
animal model: SD rats are subjected to transient middle cerebral artery occlusion and reperfusionUp Pro-inflammatory miR-485/AIM2 Promoting SK-N-SH and SH-SY5Y cells pyroptosis and inflammation Liang et al., 2020 Traumatic brain injury Cell model: microglia cells are treated with LPS+ATP Up Pro-inflammatory miR-7a-5p/NLRP3 Promoting microglial activation and inflammation Meng et al., 2021 Alzheimer's disease Animal model: the right ventricl of SD rat is injected with Aβ25-35 Down Anti-inflammatory PI3K/AKT Improving cognitive impairment; alleviating neuronal damage; inhibiting activation of astrocytes Yi et al., 2019 XIST Epilepsy Cell model: CTX-TNA2 astrocyte cells are treated with LPS;
animal model: SD rats are injected with pentylenetetrazolUp Pro-inflammatory miR-29c-3p/NFAT5 Promoting neuronal apoptosis and glutamate accumulation Zhang et al., 2021c Neuropathic pain Animal model: the bilateral sciatic nerves of SD rats are ligated Up Pro-inflammatory miR-544 /STAT3 Promoting the development of neuropathic pain and neuroinflammation Jin et al., 2018b Neuropathic pain Animal model: the bilateral sciatic nerves of SD rats are ligated Up Pro-inflammatory miR-150/ZEB1 Promoting the development of neuropathic pain and neuroinflammation Yan et al., 2018 GAS5 Parkinson’s disease Cell model: microglia cells are treated with LPS;
animal model: C57BL/6 mice are injected with rotenoneUp Pro-inflammatory miR-223-3p/NLRP3 Promoting microglial inflammation Xu et al., 2020 Spinal cord ischemia reperfusion Animal model: the aortic arch is clamping distal to the left subclavian artery and left carotid artery of the SD rat; the clamp is removed and reperfusion is continued Up Pro-inflammatory MMP-7/cleaved caspase-3 Promoting apotosis and inflammation; aggravating functional impairment Zhang et al., 2021d Multiple sclerosis Animal model: C57BL/6 mice are injected with MOG35-55 and Pertussis toxin in PBS Up Pro-inflammatory PRC2/IRF4 Inhibiting microglial M2 polarization; exacerbating demyelination Sun et al., 2017 UCA1 Epilepsy Cell model: CTX-TNA2 cells are treated with IL-1β;
animal model: SD rats are injected with pilocarpine hydrochlorideDown Anti-inflammatory miR-203/MEF2C/NF-κB Inhibiting inflammation; improving CTX-TNA2 cells viability Yu et al., 2020b Parkinson’s disease Animal model: the medial forebrain bundle of the Wistar rat is injected with 6-OHDA Up Pro-inflammatory PI3K/AKT Promoting dopaminergic neurons apoptosis, oxidative stress and inflammation Cai et al., 2019 GM4419 Ischemic stroke Cell model: primary microglial cells are placed in an oxygen and glucose deprivation condition and reperfusion Up Pro-inflammatory IkBa/NFκB Promoting microglial cell death and necrosis Wen et al., 2017 Traumatic brain injury Cell model: primary mouse astrocytes are mechanically stretch-injured using 94A Cell Injury Controller Up Pro-inflammatory miR-466l/TNF-a Promoting astrocyte apoptosis Yu et al., 2017
In this issue
Jump to section
Related Articles
Cited By...
More in this TOC Section
Similar Articles
Advertisement