Long non-coding RNA 9969 (lncRNA-9969)

Long non-coding RNA 9969 (lncRNA-9969), specifically identified as the human transcript ENST00000629969, is a functional RNA molecule that has emerged as a novel therapeutic mediator for Alzheimer’s disease. It is prominently enriched in exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs), which serve as specialized delivery vehicles to the central nervous system. Mechanistically, lncRNA-9969 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-6361 (miR-6361), thereby relieving the suppression of downstream targets within the mTOR-autophagy signaling pathway. This activation enhances neuronal autophagy, promoting the clearance of neurotoxic amyloid-beta plaques and providing robust neuroprotection against cellular damage. Furthermore, lncRNA-9969 facilitates a shift in microglial polarization from a pro-inflammatory state to a neuroprotective M2 phenotype, reducing neuroinflammation and suppressing pyroptosis. Although it represents a promising multi-target strategy for neurodegeneration, its therapeutic development involves challenges related to delivery precision and the potential for off-target effects within complex cellular RNA networks.

Other names

lnc-9969ENST00000629969Long intergenic non-protein coding RNA 9969lncRNA-0021 (murine homolog)

Acts as a competing endogenous RNA (ceRNA) by sequestering microRNA-6361 (miR-6361), thereby activating the mTOR/p70S6K signaling pathway to enhance neuronal autophagy and modulate microglial polarization toward a protective M2 phenotype.