Table 1.

Selected lncRNAs and Their Altered Expression in Memory Related Conditions lncRNA Description Regulation

lncRNA	Description	Regulation	Associated disease	Related Biological Processes	Functions & Implications	References
*17A*	LncRNA 17A	Up	AD	Cognitive decline, neurodegeneration	Regulates alternative splicing and signaling. Linked to Aβ secretion and elevation of Aβ42 production. Dysregulation leads to deactivation of GABAB signaling, autophagy and neurodegeneration.	^246–248
*ANRIL*	Antisense Noncoding RNA in The INK4 Locus (CDKN2BAS1)	Up	AD	Neurodegeneration	Regulates gene transcription repression. Involved in chromatin modifications via PRC2 recruitment.	^249–251
*BACE1-AS*	Beta-Secretase 1-Antisense RNA	Up	AD	Neurodegeneration, protein aggregation	Involved in post-transcriptional regulation and BACE1 mRNA stability, competes with miR-485–5p for binding to BACE1 and prevents it’s targeting on BACE1 mRNA. Increases Aβ 1–42 accumulation.	^252–255
*BC1*	LncRNA BC1 (BC1-FMRP)	Up	AD	Spatial learning and memory impairments, protein aggregation	Involved in mRNA translation and downregulation of BC1. Leads to accumulation of Aβ peptides.	^{227,256–259}
*BC200*	LncRNA BC200	Soma: Up Dendritic: Down	AD	Cognitive decline	Regulates local translation at the synapse, long-term synaptic plasticity and enhances BACE1 and Aβ1–42 expression.	^{256–258,260–263}
*EBF3-AS*	Early B Cell Transcription Factor 3-Antisense RNA	Up	AD	Neurodegeneration	Promotes neuronal apoptosis through Aβ25–35- and okadaic acid.	²⁶⁴
*GDNF-AS1*	Glial Cell Derived Neurotrophic Factor (GDNF Antisense RNA 1)	--	AD	Neurodegeneration	Involved in mRNA translation.	²⁰⁶
*GDNF-AS*	Glial Cell Derived Neurotrophic Factor -Antisense RNA	down	PD	Cognitive decline; neurodegeneration	Involved in mRNA stability.	²⁶³
*LRP1‐AS*	LDL Receptor Related Protein 1-Antisense RNA	Up	AD	Cognitive decline. neurodegeneration	Transcription repression by sequestration of chromatin-regulatory proteins. Linked to the increasing Aβ formation and decreased clearance. Regulate LRP1 expression.	^265–268
*MEG3*	Maternally Expressed 3	Down	AD	Cognitive decline, Involved with spatial learning and memory ability	Upregulation of MEG3 inhibits the pathological injury and hippocampal neurons apoptosis, decreased Aβ expression, inhibited oxidative stress and inflammatory injury. Involved in induced astrocytes activation through blocking PI3/Akt pathway.	²²⁶
*MEG3*	Maternally Expressed 3	Down	HD	Neurodegeneration	Involved in gene regulation. MEG3 is a direct target of REST and modulate mHTT aggregation.	^{251,269–271}
*NEAT1*	Nuclear Paraspeckle Assembly Transcript 1	Up	AD	Cognitive decline	Essential for Paraspeckles formation, integrity, gene expression regulation and miRNA sponging.	²⁸
*NEAT1, NEAT1-L, NEAT1-S*	Nuclear Paraspeckle Assembly Transcript 1	Up	HD	Cognitive decline	Decreasing NEAT1 expression lowers mHTT aggregates and TP53 expression in HD. NEAT1 provides neuroprotection against mHtt-induced cytotoxicity NEAT1-L) and oxidative stress-induced injury NEAT1-S).	^{251,271–273}
*NEAT1*	Nuclear Paraspeckle Assembly Transcript 1	Up	PD	Cognitive decline	Upregulation of NEAT1 supports Bax/BCl ratio, caspase 3 activity, α-synuclein expression, MPTP concentration, LC3-II/LC3-I level and promotes PINK1 protein stability. NEAT1 serves as miR-124 decoy and promotes cell death and apoptosis.	^{251,274–276}
*MIAT*	Myocardial Infarction Associated Transcript	Down	AD	Cognitive decline, Neurodegeneration, Protein aggregation	MIAT regulates Aβ clearance through LRP1 expression. Downregulation of MIAT promotes miR-150–5p/VEGF-mediated fibrillogenesis, reduces the number of microvessels and the expression of tight junction proteins. Loss of MIAT increases Aβ40 and Aβ42 levels and promotes neuronal loss.	^251,277
**NAT-RAD18**	Natural antisense transcript against RAD18 E3 Ubiquitin Protein Ligase	Up	AD	Neurodegeneration	Promotes neuron loss through the down regulation of RAD18 expression.	²⁷⁸
*NDM29*	Neuroblastoma Differentiation Marker 29	Up	AD	Neurodegeneration, Protein aggregation	Promotes Alu-induced inflammation and processing of APP and amyloid β secretion.	^247,279
*SORL1-AS*	Sortilin Related Receptor 1-Antisense RNA	Up	AD	Protein aggregation, Cognitive decline	Decreases SORL1 expression by altering mRNA splicing and impairs APP processing.	^251,280
*SOX2-OT*	SRY-Box Transcription Factor 2-Overlapping Transcript	Up	AD, PD	Neurodegeneration	Regulates co-transcribed Sox2 gene expression, reduces Frizzled 3/5 FZD3/5)-mediated Wnt signaling and triggers oxidative stress generation that leads to apoptosis and neuronal loss.	^281,282
*HAR1A, HAR1F*	Highly Accelerated Region 1A, F	Down	HD	Neurodegeneration	Direct targets of REST. Mutated huntingtin gene lead to abnormal nuclear-cytoplasmic REST/NRSF trafficking leading to downregulation of HAR1 expression and subsequently repression of numerous neuronal genes.	^{251,283–286}
*HTT-AS*	HTT Antisense RNA	Down	HD	--	Overexpression of HTT-AS downgrades endogenous HTT transcript levels.	^248,287
*LINC003 41*	SYNE3: Spectrin Repeat Containing Nuclear Envelope Family Member 3	Up	HD	--	Unknown	^251,269
*LINC003 42*	Long Intergenic Non-Protein Coding RNA 342	Down	HD	--	Unknown	^251,269
*RPS20P 22*	Ribosomal Protein S20 Pseudogene 22	Up	HD	--	RPS20P22 regulates RPS20 expression. Reduction of RPS20P22 leads to accumulation of p53.	^251,269
*TUG1*	Taurine Up-Regulated 1	Up	HD, Aging	Cognitive decline, neurodegeneration	Direct downstream target of p53. Binds to the PRC2 epigenetic regulatory complex of genes and sponge/decoy function.	^250,288,289
*TUNA (TUNAR)*	Tcl1 Upstream Neuron-Associated lincRNA	Down	HD	--	TUNA expression declines significantly with increased HD disease grade.	^251,290
*HOTAIR*	HOX Transcript Antisense RNA	Up	PD	Neurodegeneration	HOTAIR upregulation is associated with LRRK2 upregulation and the induction of caspase 3-dependent apoptosis.	^291–293
*MALAT1*	Metastasis Associated Lung Adenocarcino ma Transcript 1	Up	PD	Neurodegeneration	Involved in synapse development by regulating synapse formation and maintenance of genes expression. Modulates the recruitment of SR family pre-mRNA-splicing factors to the transcription site.	^294,295
*MALAT1*	Metastasis Associated Lung Adenocarcino ma Transcript 1	--	AD	Neurodegeneration	Negatively regulates the CDK5R1/p35 complex and promotes cell death by controlling expression of the miR-15/107 family.	^217,251
*NORAD*	Non-Coding RNA Activated by DNA Damage	Down	PD	---	NORAD stabilizes the genome through PUMILIO proteins. Downregulation of NORAD induces cytotoxicity through caspase3/7, ROS and LDH activity.	^251,296
P21	Long non-coding RNA-p21	Up	PD	Neurodegeneration	p21 is a miR-1277–5p decoy and regulates α-Synuclein through miR-1277–5p. Upregulation of p21 inhibits cell viability, promotes caspase 3 activation, and increases Bcl family-initiated apoptosis.	^297,298
*PINK1-AS*	PTEN Induced Kinase 1-Antisense RNA	Up	PD	Neurodegeneration	Regulates the stability of Pink1 transcript, involved in mitochondrial biogenesis and increases the sensitivity to apoptosis.	²⁹⁹
*SNHG1*	Small Nucleolar RNA Host Gene 1	Up	PD	Neurodegeneration	Upregulation of SNHG1 promotes neuroinflammation.	^300–302
*SNHG1*	Small Nucleolar RNA Host Gene 1	Down	PD	Neurodegeneration	Involved in miR-15 decoy and inhibits miR-15 function.	^268,303
*UCHL1-AS1*	Ubiquitin C-Terminal Hydrolase L1-Antisense RNA 1	Down	PD	Neurodegeneration	Involved in dopaminergic neuron differentiation and maintenance, cellular stress response and miRNA decoy. Promotes Uchl1 expression by upregulating the translation process.	^304–306
*RMST*	Rhabdomyosar coma 2-associated Transcript	--	--	Neurogenesis, Neurodegeneration	Transcriptionally repressed by REST, required for the binding of SOX2 to promoter regions of neurogenic transcription factors and involved in neurogenesis.	³⁰⁷
*GAS5*	Growth-arrest-specific 5	up	Aging	Cognitive decline, neurodegeneration	Prepares the cell to apoptosis. Upregulation correlates with impaired learning and novelty-induced behavior.	^308–310
*DGCR5*	DiGeorge syndrome critical region gene 5	Down	HD	Neurodegeneration	DGCR5 is downstream target of REST in HD disease.	^269,311,312