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Target intelligence / Profile preview
Low-density lipoprotein receptor-related protein 1 antisense RNA (LRP1-AS)
- Target
- LRP1-AS
- Molecular classification
- Long non-coding RNA (lncRNA), Natural antisense transcript (NAT), Other: Antisense RNA
01
Overview
Low-density lipoprotein receptor-related protein 1 antisense RNA (LRP1-AS) is a long non-coding natural antisense transcript (NAT) arising from the LRP1 gene locus. LRP1-AS negatively regulates the expression of the LRP1 gene through direct interaction with the chromatin protein HMGB2, inhibiting HMGB2’s ability to activate LRP1 transcription. LRP1-AS and LRP1 mRNA can form RNA duplex structures that further modulate their function. In Alzheimer’s disease brain tissue, LRP1-AS levels are elevated while LRP1 levels are decreased, suggesting a disease-relevant regulatory role. Synthetic antisense oligonucleotides ("antagoNATs") targeting LRP1-AS can disrupt its interaction with HMGB2 and restore LRP1 expression, indicating therapeutic potential for neurodegenerative disorders. LRP1-AS is an emerging target and biomarker in disease contexts tied to LRP1 dysregulation and chromatin-mediated transcriptional control[1][3].
- Other names
- LRP1 antisense RNALRP1-ASRP11-545N8.3sloty
02
Mechanism of action
Inhibition of LRP1-AS using antisense oligonucleotides ("antagoNATs") increases LRP1 expression by preventing LRP1-AS–HMGB2 interaction
03
Biological functions
Regulation of gene expression via antisense interactionNegative regulation of LRP1 mRNA expressionModulation of chromatin-associated protein (HMGB2) activityFormation of RNA duplexes with sense transcripts to affect transcription
04
Disease associations
Neurodegenerative disease (Alzheimer’s disease: LRP1-AS is upregulated in AD brains and may play a role in disease progression through repression of LRP1)Potential biomarker and therapeutic target for other diseases involving dysregulated LRP1/lncRNA pathways
05
Safety considerations
Not well characterized. General concerns for lncRNA-targeted therapies include off-target effects and challenges in tissue-specific deliveryNo specific drug safety data currently available for LRP1-AS targeting agents.
06
Interacting drugs
AntagoNATs (synthetic antisense oligonucleotides targeting LRP1-AS have been developed and shown to upregulate LRP1 by disrupting the LRP1-AS/HMGB2 interaction)
07
Biomarkers
LRP1-AS (expression levels in brain can serve as a biomarker for Alzheimer’s disease and disease progression—high LRP1-AS correlates with low LRP1 in AD brain samples)
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