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. | Â | [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 | Â | 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 | ||
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 | Â | 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 | |
MALAT1, MEG3 |  | TDP43 | In iCLIP data, MALAT1 inteactes with TDP43, and FUS interactes with MEG3. | ALS patinets’ tissue extract | |||
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 | |||
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 | Â | 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 | Â | Â | 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] |