Table 3.
ncRNAs and related processes in Alzheimer’s disease
| Name | up/down regulation | genetic mutation | Description | Model | Ref | |
|---|---|---|---|---|---|---|
| LncRNAs | BC1 | up | Tg2576-APPswe | Induces APP mRNA translation via association with fragile X syndrome protein (FMRP). Induces Aβ peptides accumulation and affects spatial learning and memory impairments of mice. | mouse | [83] |
| BC200 | up | Regulate cell vialbility via directly targeting BACE1 mRNA expression. BC200 increases BACE1 expression and enhances Aβ1–42 expressioin. | AD brain section | [84–86] | ||
| LncRNA -17A | up | Aβ1–42 treatment | Upregulates autophagy, deactivates GABAB signaling and induces neurodegeneration. | neuroblastoma | [87] | |
| LncRNA -17A | up | Inducing inflammation response | Impaires GABAB signaling through mediating receptor isoform switch via altering alternative splcing, and further induce Aβ secretion and increment of Aβ42/40 ratio. | AD brain section, SH-SY5Y cells | [88] | |
| MEG3 | up | microinjection of Aβ25–35 | Inhibiting the PI3K/Akt signaling pathway and apoptosis of hippocampal neurons, decreased Aβ expression, inhibited oxidative stress injury and inflammatory injury. | rat | [89] | |
| MIAT | down | APPswe/PSEN1ΔE9 | Regulates amyloid clearance via regulating low-density lipoprotein receptor related protein 1 (LRP1) expression and miR-150-5p/VEGF mediated fibrillogenesis; Increased Aβ40 and Aβ42 levels and neuronal loss; Decreased brain microvessel number and the expression of tight junction proteins. | mouse | [90] | |
| NDM29 | up | – | Induces APP synthesis and promotes cleavage activity of BACE1 and γ-secretase. Increase Aβ secretion and increment of Aβ42/40 ratio. | AD brain section, mouse neuroblastoma | [88] | |
| NEAT1 | up | Aβ1–42 treatment | Mediates Aβ and pTau induced neuronal death via acting as miR-107 decoy. | human cell line | [91] | |
| NEAT1 | up | – | Mediates Aβ secretion and pTau via regulating miR-124/BACE1 regulation. | mouse model | [92] | |
| NEAT1 | up | – | Negetively regulating CDK5R1 mRNA level through positively regulating miR-15/107. | AD brain | [93] | |
| P3Alu/SINE | up in RPE | – | Neurodegeneration via P3Alu-induced inflammasomes (in RPE; still a hypothesis in neurons) | AD brain section, mouse model | [94] | |
| NATs | BACE1-AS | up | APP-KM670/ 671NL and V717F | Stabilizes BACE1 mRNA and prevents miR-485-5p targeting on BACE1 mRNA. Increased Aβ42 is identified in the models. | AD brain section, mouse | [95, 96] |
| BDNF-AS | up | – | In epigenetic level, promots BDNF depletion. | mouse model, HEK293T | [33] | |
| EBF3-AS | up | APPswe/PSEN1ΔE9, Aβ25–35 treated cell | Reduces EBF3 (early B cell factor 3) expression and promots cell death. | mouse model, cell | [97] | |
| SORL1-AS(51A) | up | – | SORL1-AS is the antisense orientation in intron 1 of the SORL1 gene and decrease SORL expression via altering splicing. SORL1-AS overexpression results in impaired processing of APP and increased Aβ formation. | AD brain section | [98] | |
| SOX21-AS1 | up | Aβ1–40 treatment | Reducing Frizzled 3/5 (FZD3/5) mediated Wnt signaling pathwa and trigged oxidative stree and cell death in hippocampal neurons. | mouse model | [99] | |
| NAT-RAd18 | up | Aβ1–40 treatment | Promotes DNA damage via reducing Rad18 expresion, and leads to cell death. | Rat cortical neurons | [100] | |
| LRP1-AS | up | – | Disrupts LRP1 mediated Aβ clarance via directly binding to high-mobility group box 2 (Hmgb2) and blocking the Srebp1a-dependent transcription of LRP1. Promotes APP endocytic trafficking, increases Aβ formation and decreases Aβ clearance. | AD brain section, Hmgb2 KO mice and mouse RAW264.7 cell line | [101, 102] | |
| EBF3-AS, HAO2-AS, AD-lic1, AD-linc2 | up | – | Promoting neuron apoptosis. | AD brain section | [103] | |
| microRNAs | let-7b | up | – | Activating RNA-sensing Toll-like receptor 7 and neuronal death. | AD CSF, mouse model, macrophages | [104] |
| miR-106b | up | Tg-APPswe/PSΔE9 | Regulate TGF-β signaling pathways and reduce phosphprylation of Smad2/3 and smad6/7 for promoting neurodegenration. | mouse models | [105] | |
| miR-106b | down | – | Regulates tau phosphoryation via targeting Fyn (tyrosine kinase) and increase pTau. | AD brain section, human cell line | [106] | |
| miR-128 | up | 3xTg-AD | Reducing APP expression, Aβ production and inflammatory response via tardeting peroxisome proliferator-activated receptor gamma (PPARγ) expression. | mouse model | [107] | |
| miR-34a, mIr132/212 | down | 3x Tg-AD (PSEN1(PS1M146V), APP (APPSwe) and Tau (P301L) | Correlated with Aβ production via targeting Sirt. Sirt can regulate Aβ production. | mouse model | [108, 109] | |
| miR-132/212 | down | 3x Tg-AD (PSEN1(PS1M146V), APP (APPSwe) and Tau (P301L) | Regulating Tau expression via direct interaction and association with GSK-3β and PP2B mediated tau phosphorylation. | AD brain section, mouse model, mouse neuroblastoma | [110] | |
| miR-142a-5p, miR-146a-5p, miR-155-5p, miR-455-5p | up | APPswe/PS1L166P, THY-Tau22 | May be part of a protective response in AD. | AD brain section, mouse model | [110] | |
| miR-15/107 | down | – | Increase expression of CDK5R1/p35 and consequently enhance CDK5 activity. miR-15/107 also modulates BACE1 expression and increase APP protein expresin and pTau formation. | AD brain section, human cell lines | [111, 112] | |
| miR-16 | down | Attenuate Aβ mediated neurotoxicity via reducing BACE1 expression. | post morten tissue | [113] | ||
| miR-200b/c | up | Aβ treatment/ Tg2576 transgenic mice | miR-200b/c inhibits S6K1-dependent phosphorylation of IRS-1, suppresse IRS-1pSer signaling pathway and cause insulin resistance in the brain. Aβ secretion is corelated in the models. | mouse model, mouse cell lines | [114] | |
| miR-25 | up | Aβ1–42 induction | Downregulating KLF2 via Nrf2 signaling pathway to suppress proliferation and promot apoptosis. | mouse model | [115] | |
| miR-29a/b-1 | down | – | Decreases BACE1 expression. | AD brain section | [116] | |
| miR-29c | down | – | Regulating the expression of BACE1 by directly targeting its 3’UTR and promoting cell proliferation via PKA signaling. Increasing BACE1 level via PKA/CREB signaling pathway. | Peripheral blood of AD pateints, SAMP mouse model | [117] | |
| miR-33 | deletion | miR-33(−/−); APPswe/PSEN1ΔE9, | Increasing ATP-binding cassette transporter A1 (ABCA1) expression, ApoE lipidation, and decreaseing Aβ level. | mouse and human neural cells | [118] | |
| miR-34a | up | APPswe/PSEN1ΔE9 | Regulating γ-secretase activity, BACE1 expression and lead to increasing Aβ level. Interacting with the 3′-UTR of bcl2 mRNA and inhibiting bcl2 translation, and increasing caspase 3 activity. | mouse model | [119, 120] | |
| miR-485-5p | down | – | miR-485-5p is corelated to BACE1 upregulation. The expression of two competitively regulatory RNAs, miR-485-5p and BACE1-AS, are dysregulated. | AD brain section | [96] | |
| miR-873-5p | down | Aβ1–42 induction | Preveting apoptosis via targeting Heme oxygenase 1 (HMOX1) expression level. | mouse model, rat cell line | [121] | |
| miR-338-5p | down | 5XFAD transgenic (TG) mice | Mediaing amyloid formation via targeting BACE1; associtaed with NF-kB signaling pathway activation. Doenregulated miR-338-5p increases BACE1 expression, Aβ formation, and neuroinflammation. | AD brain section, mouse | [122] |