Role of Long Noncoding RNAs in Parkinson’s Disease: Putative Biomarkers and Therapeutic Targets

Table 1

LncRNAs: their mechanism of action in Parkinson’ disease.

lncRNA	Tissue/model	Regulation	Pathway targeted by the lncRNAs	References
AS UCHL1	(1) MN9D cells treated with MPP+	Down	AS Uchl1 RNA, as a component of Nurr1-dependent gene network and target of cellular stress, extended the understanding on the role of antisense transcription in the brain	[28]
	(2) DA neurons from PD model treated with MPP+
HAGLROS	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	Suppression of HAGLRO decreased apoptosis and autophagy in both in vivo and in vitro PD models	[29]
			HAGLRO negatively regulated miR-100 expression
			Suppression of HAGLROS alleviated MPP(+)-intoxicated SH-SY5Y cell injury by activating PI3K/AKT/mTOR pathway
HOTAIR	SH-SY5Y cells treated with MPP+	Up	With HOTAIR overexpression in SH-SY5Y cells, the expression of LRRK2 increased compared with that in the control	[30]
			HOTAIR knockdown provided protection against MPP(+)-induced DA neuronal apoptosis by repressing caspase 3 activity
MALAT1	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	MALAT1 knockdown attenuated MPTP-induced apoptosis of DA neurons in MPTP-induced PD mouse model	[31]
			MALAT1 interacted with miR-124 to negatively regulate its expression
	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	MALAT1 was associated with a-synuclein, leading to the increased stability of a-synuclein and its expression	[32]
	MPTP-induced PD mice and MN9D cells treated with MPP+	Up	MALAT1/miR-205-5p axis regulates MPP(+)-induced apoptosis in MN9D cells by targeting LRRK2	[33]
	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	MALAT1 knockdown attenuated MPP(+)-induced apoptosis of DA neurons in SH-SY5Y cells	[34]
			MALAT1 regulates DAPK1 expression by targeting miR-124-3p
MAPT-AS1	Brain tissue samples (10 patients with PD and 10 controls)	Down	MAPT-AS1 and DNMT1 have been identified as potential epigenetic regulators of MAPT expression in PD	[35]
Mirt2	SY5Y cells treated with TNF-α	Down	Mirt2 exhibited anti-inflammatory properties through miR-101 suppression	[36]
			Mirt2 blocked TNFα-triggered NF-κB/p38MAPK pathway
NEAT1	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	NEAT1 knockdown promoted cell viability and suppressed cell apoptosis	[37]
			Downregulation of NEAT1 also decreased the ratio of Bax/Bcl-2, the activity of caspase-3, as well as the expression of α-synuclein
	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	NEAT1 positively regulated the protein level of PINK1 through inhibition of PINK1 protein degradation	[38]
			NEAT1 knockdown could effectively suppress MPTP-induced autophagy that alleviated dopaminergic neuronal injury
lincRNA-p21	SH-SY5Y cells treated with MPP+	Up	lincRNA-p21 regulated MPP(+)-induced neuronal injury by sponging miR-625 and upregulating TRPM2 in SH-SY5Y cells	[39]
	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	lincRNA-p21 sponged miR-1277-5p and indirectly increased the expression of α-synuclein to suppress viability and activate apoptosis in SH-SY5Y cells	[40]
	MPTP-induced PD mice and SH-SY5Y cells treated with a CM transfer system were used to determine the impact of LPS-treated BV2 cells	Up	p53/lincRNA-p21, together with miR-181/PKC-δ, formed a double-negative feedback loop that facilitated sustained microglial activation and the deterioration of neurodegeneration	[41]
SNHG1	MPTP-induced PD mice and SH-SY5Y cells treated with MPP+	Up	SNHG1 could directly bind to miR-15-5p and repress miR-15-5p expression	[42]
			Upregulation of miR-15b-5p alleviated α-synuclein aggregation and apoptosis by targeting SIAH1
			SNHG1 knockdown inhibited α-synuclein aggregation and α-synuclein-induced apoptosis
	MN9D cells treated with MPP+	Up	SNHG1 could competitively bind to the miR-221/222 cluster and indirectly regulate the expression of p27/mTOR	[43]
	SH-SY5Y cells treated with MPP+	Up	SNHG1 overexpression lowered viability and enhanced apoptosis in MPP(+)-treated SH-SY5Y cells.	[44]
H19	MPTP-induced PD mice and human neuroblastoma cells treated with MPP+	Down	H19 attenuates apoptosis in MPTP-induced Parkinson's disease	[45]
			H19/miR-585-3p axis regulates MPP(+)-induced apoptosis in human neuroblastoma cells cells by targeting PIK3R3
UCA1	6-OHDA-induced PD rat	Up	Downregulation of lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in PD rats	[46]
			Downregulation of lncRNA UCA1 inhibits the PI3K/Akt signaling pathway.