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bioRxiv · 10.1101/2024.03.27.583257

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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Abstract

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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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.. 2024-03-27. Circular RNA aptamers ameliorate AD-relevant phenotypes by targeting PKR. https://doi.org/10.1101/2024.03.27.583257

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