Table 3 ncRNAs and related processes in Alzheimer’s disease

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]