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Table 4 ncRNAs and related processes in other neurodegenerative diseases

From: Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

Disease

ncRNA class

Name

up/down regulation

Mutation

Description

Model

Ref

ALS

NATs

IER3-AS, ZBTB11-AS, PAXBP-AS, SNAP25-AS, CKMT2-AS,

down, down, up,down, down

SALS, TDP43, SOD1, FUS

IER3-AS and ZBTB11-AS downregulated in sporadic ALS; PAXBP-AS upregulaed in ALS-FUS; SNAP25-AS downregulated in ALS-FUS; CKMT2-AS downregulated in ALS-SOD1. The mechnisms are still unkown.

ALS spinal cord extract, peripheral blood mononuclear cells

[140]

LncRNAs

ncRNACCND1

up

FUS/TLS

In response to DNA damage, ncRNACCND1 interactes with FUS and represses CCND1 transcription by enhancing inhibition of CBP and p300 histone acetyltransferase activities.

 

[137]

tiRNAs (tRNA-derived RNA fragments)

up

ANG-P112L

tiRNAs inhibit translation via its G-guadruplex structure. tiRNAs displace eIF4 from mRNA and stablizes YB-1. tiRNAs promotes the untranslated mRNA for stress granule formation.

cell line

[136]

Lhx1as, LncMN-1, LncMN2

 

Fus P517L

detected in mouse model without know mechanisms.

mouse

[138]

MicroRNAs

miR-17~92

down

SOD1G93A; SOD1L144F

miR-17~92 cluster target E3 ubiguitin ligase to regulate PTEN subcellular location via monoubiquitination. miR-17~92/nuclear PTEN regulats motor neuron vulnerability in SOD1ALS.

ALS patienst’s iPSC, mouse model

[145, 146]

miR-155

up

SOD1G93A

miR-155 distributes in rodent and patients’ spinal cord. Anti-miR-155 treatement improve survival rate by mainly blocking miR-155 funcion in microglia, astrocyte and neuron.

ALS spinal cord, rodent model

[147]

miR-155

up

SOD1G93A

miR-155 regulates survival gene expression in microglia incuding P2ry12, Tmem119, Olfml3, Egr1, Atf3, Jun, Fos, and Mafb and Tgfbr1 .

ALS spinal cord, rodent model

[22]

miR-206

down

 

miR-206 contols HDAC4 expression in neuromuscular gene expression and restore the NMJ function.

mouse model

[149]

miR-218

up

SOD1G93A

miR-218 can be transported from motor neurons to neighbouring astrocytes and sufficiently downregulates glutamate transporter in astrocytes (excitatory amino acid transport 2 (EAAT2)). Blocking miR-218 with antisense oligonucleotides recover EAAT2 expression and mitigates astrogliosis in mouse brain.

mouse model

[148]

miR-375-3p

down

Vps54

tumor suppressor gene NDRG2 and miR-375-3p are dysregulated in sporadic ALS. Upregulated NDRG2 increas ROS formation and further activates p53. Insufficient targeting p53 by miR-365-3p leads to NDRG2 and ROS upregulation.

ALS-iPSC

[143]

miR-375

down

FUSP525L

miR-375 targets p53 and ELAVL4, which are upregulated due to loss of FUS function.

ALS-iPSC

[144]

miR-92a-3p, miR-125b-5p,

down

 

miR-92a-3p and miR-125b-5p target NEFM 3’UTR .

ALS spinal cord

[142]

miR-124-3p, miR-92a-3p, miR-20b-5p miR-223b-3p,

down

 

miR-124-3p, miR-92a-3p, miR-20b-5p and miR-223b-3p target NEFH 3’UTR.

ALS spinal cord

[142]

ALS; FTLD

LncRNA

C9ORF72 (repeat expansion)

up

hexanucleotide repeat expansion in C9orf72 intron 1

HRE repeats expansion disrupts RAN dependent protein/RNA nucleaocytoplasmic transport by sequestering RNAGAP1 and leads to neurodegeneration. HRE also get translated into toxic dipeptide by interacting with PAC1 depedent translation factor and leads to neurodegeneration.

ALS patients’ brain, spinal cord; iPSC, mouse, fly

[129, 130]

MALAT1, MEG3

 

TDP43

In iCLIP data, MALAT1 inteactes with TDP43, and FUS interactes with MEG3.

ALS patinets’ tissue extract

[132, 133]

NEAT1

up

TDP43, FUS

NEAT1_2 interacte with TDP43 and FUS by iCLIP data. TDP43 and FUS are recruited to paraspeckle due to interaction with NEAT1_2.

ALS patients’ tissue extract

[132–135]

snRNA

U12 snRNA, Hsrw

up

TDP43

associated with neurodegeneration caused by TDP43 promoted transcrption elongation via interaction with ELL2 in elongation complexes.

Fly

[131]

SMA

snRNA

variant of U1 snRNA (vU1)

up

 

variant of U1 snRNA (vU1) is upregulated and affects U1 snRNA expression. The ratio of vU1/U1 increased in SMA-iPSC derived MN compared with control.

SMA-iPSC

[150]

SCA2

NATs

ATXN2-AS

  

ATXN1-AS transcripts with CAG repeats forms RNA foci and detected in SCA2 cerebellar Purkinje cell. ATXN1-AS and CAG repeats trigger caspase 3/7 dependent apoptosis.

SCA2 tissues

[151]