Circular RNA aptamers ameliorate AD-relevant phenotypes by targeting PKR
Feng, X.; Jiang, B.-W.; Zhai, S.-N.; Liu, C.-X.; Wu, H.; Zhu, B.-Q.; Wei, M.-Y.; Wei, J.; Yang, L.; Chen, L.-L.
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Here, we delineated the remarkably elevated neuroinflammation accompanied by progressive activation of double-stranded RNA (dsRNA)-activated Protein Kinase R (PKR) and PKR-related dsRNA pathways in hippocampus of 5xFAD mice upon Alzheimers disease (AD) progression. AAV-delivery of circular RNAs possessing short-imperfect duplex regions (ds-cRNAs) to neurons and microglia effectively dampened excessive PKR activity with little toxicity, accompanying with reduced neuroinflammation and amyloid-beta (A{beta}) plaques, resulting in neuroprotection and enhanced capability of spatial learning and memory in AD mouse models. These findings suggest a therapeutic potential of ds-cRNA aptamers as PKR inhibitors in AD therapy.
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