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The Expanding Regulatory Mechanisms and Cellular Functions of Long Non-coding RNAs (lncRNAs) in Neuroinflammation

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Abstract

LncRNAs have emerged as important regulatory molecules in biological processes. They serve as regulators of gene expression pathways through interactions with proteins, RNA, and DNA. LncRNA expression is altered in several diseases of the central nervous system (CNS), such as neurodegenerative disorders, stroke, trauma, and infection. More recently, it has become clear that lncRNAs contribute to regulating both pro-inflammatory and anti-inflammatory pathways in the CNS. In this review, we discuss the molecular pathways involved in the expression of lncRNAs, their role and mechanism of action during gene regulation, cellular functions, and use of lncRNAs as therapeutic targets during neuroinflammation in CNS disorders.

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Abbreviations

AD :

Alzheimer’s disease

ALS:

amyotrophic lateral sclerosis

ANRIL:

antisense non-coding RNA in the INK4 locus

APP :

amyloid precursor protein

Aβ:

amyloid beta

BACE1:

β-site amyloid precursor protein cleaving enzyme 1

BBB:

blood-brain barrier

BDNF:

brain-derived neurotrophic factor

BMECs:

brain microvascular endothelial cells

C2dat1 :

CAMK2D-associated transcript 1

CCAT1:

colon cancer–associated transcript-1

CCL2:

C-C motif chemokine ligand 2

ceRNAs:

competing endogenous RNAs

CNS :

central nervous system

CRNDE:

colorectal neoplasia differentially expressed

DGCR5:

DiGeorge syndrome critical region gene 5

DILC:

LncRNA downregulated in liver cancer stem cells

DM:

diabetes mellitus

DRG:

dorsal root ganglion

EAE:

experimental autoimmune encephalomyelitis

EBI:

early brain injury

EZH2:

enhancer of zester homolog 2

FAL1:

focally amplified lncRNA on chromosome 1

FIRRE:

functional intergenic repeating RNA element

FosDT:

Fos downstream transcript

FUS:

fused in sarcoma

GAS5:

growth arrest-specific 5

GBM:

glioblastoma multiforme

GBP9:

LncRNA guanylate binding protein-9

GFAP:

glial fibrillary acidic protein

GO:

gene ontology

HIV-1:

human immunodeficiency virus

HMGB-1:

high mobility group box-1

HnRNP-A2/B1:

heterogeneous nuclear ribonucleoprotein A/B and A2/B1

I/R:

ischemia and reperfusion

ICH:

intracerebral hemorrhage

IFN-γ:

interferon-gamma

IL-1β :

interleukin-1β

IL-6 :

interleukin-6

iNOS:

inducible nitric oxide synthases

KEGG:

Kyoto Encyclopedia of Genes and Genomes

lincRNAs:

long intergenic non-coding RNAs

lncRNAs:

long non-coding RNAs

LPS:

lipopolysaccharide

Maclpil:

macrophage contained LCP1-related pro-inflammatory

MALAT1:

metastasis-associated lung adenocarcinoma transcript 1

MAPK :

mitogen-activated protein kinase

MCAO:

middle cerebral artery occlusion mouse

MCP-1:

monocyte chemoattractant protein-1

miRNAs:

microRNAs

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MS :

multiple sclerosis

Mtss1:

metastasis suppressor-1

ncRNAs:

non-coding RNAs

NDM29:

neuroblastoma differentiation marker 29

NEAT1:

nuclear paraspeckle assembly transcript 1

NF-κB:

nuclear factor-k-gene binding

NKILA:

NF-κB interacting lncRNA

NLRP3:

Nod-like receptor protein 3

NO:

nitric oxide

NRON:

non-coding repressor of nuclear factor of activated T cells

OGD/R:

oxygen glucose deprivation/reoxygenation

PCAI:

protect cells from apoptosis and inflammation

PD:

Parkinson’s disease

PI3K :

phosphoinositide 3-kinase

PKC:

protein kinase C

PRC2:

polycomb repressive complex 2

RGCs:

retinal ganglion cells

RMST:

rhabdomyosarcoma 2–associated transcript

ROS:

reactive oxygen species

SAE:

sepsis-associated encephalopathy

SAH:

subarachnoid hemorrhage

SCI:

spinal cord injury

siRNAs:

small interfering RNAs

SNL:

spinal nerve ligation

SOCS3:

suppressor of cytokine signaling 3

SOD1:

superoxide dismutase 1

STAT6:

signal transduction and activators of transcription 6

TAK1:

TGF-β-activated kinase 1

TARDBP:

transactive response DNA binding protein

TBI:

traumatic brain injury

TGF-β:

transforming growth factor

TLE:

temporal lobe epilepsy

TNF-α :

tumor necrosis factor-α

TUG1:

taurine-upregulated gene 1

VEGF:

vascular endothelial growth factor

XIST:

X inactive specific transcript

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Acknowledgments

Figure 1 was created with BioRender.com. This work is supported by extramural grants from the Government of India, DBT-BT/PR27371/MED/122/122/2017 to VS and AB; DST Grant No. DST-SERB ECR/2017/001953 and DBT-RLS 102/IFD/SAN/3499/2016-17 to VS; OPERA award from BITS Pilani to VS. BS was supported by a scholarship from BITS Pilani and ICMR SRF. Swati acknowledges DST, New Delhi, for providing fellowship (DST/INSPIRE Fellowship/2019/IF190343).

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  1. Shraddha Tripathi and Bakhya Shree contributed equally to this work

Authors and Affiliations

  1. Department of Biological Sciences, Birla Institute of Technology and Science, Pilani-Hyderabad Campus, Jawahar Nagar, Hyderabad, Telangana, 500 078, India

    Shraddha Tripathi, Bakhya Shree,  Swati & Vivek Sharma

  2. National Brain Research Centre, Manesar, Gurugram, Haryana, 122052, India

    Stuti Mohapatra & Anirban Basu

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  1. Shraddha Tripathi
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VS and AB conceived and designed the manuscript. ST, BS, SM, S, AB, and VS wrote the manuscript. All authors read and approved the final version of the manuscript.

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Tripathi, S., Shree, B., Mohapatra, S. et al. The Expanding Regulatory Mechanisms and Cellular Functions of Long Non-coding RNAs (lncRNAs) in Neuroinflammation. Mol Neurobiol 58, 2916–2939 (2021). https://doi.org/10.1007/s12035-020-02268-8

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