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- Title
Downregulation of Ripk1 and Nsf mediated by CRISPR-CasRx ameliorates stroke volume and neurological deficits after ischemia stroke in mice.
- Authors
Xincheng Song; Yang Lan; Shuang Lv; Yuye Wang; Leian Chen; Tao Lu; Fei Liu; Dantao Peng
- Abstract
Necroptosis is implicated in the pathogenesis of ischemic stroke. However, the mechanism underlying the sequential recruitment of receptor-interacting protein kinase 1 (RIPK1) and N-ethylmaleimide-sensitive fusion ATPase (NSF) in initiating necroptosis remains poorly understood, and the role of NSF in ischemic stroke is a subject of controversy. Here, we utilized a recently emerging RNA-targeting CRISPR system known as CasRx, delivered by AAVs, to knockdown Ripk1 mRNA and Nsf mRNA around the ischemic brain tissue. This approach resulted in a reduction in infarct and edema volume, as well as an improvement in neurological deficits assessed by Bederson score, RotaRod test, and Adhesive removal test, which were achieved by RIPK1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein signaling pathway involved in neuronal necroptosis. In conclusion, the downregulation of Ripk1 mRNA and Nsf mRNA mediated by CRISPR-CasRx holds promise for future therapeutic applications aimed at ameliorating cerebral lesions and neurological deficits following the ischemic stroke.
- Subjects
BIOLOGICAL models; FLUOROIMMUNOASSAY; PROTEIN kinases; T-test (Statistics); RESEARCH funding; DESCRIPTIVE statistics; MANN Whitney U Test; ADENOSINE triphosphatase; RNA; MICE; CELL lines; ISCHEMIC stroke; CELL death; ANIMAL experimentation; WESTERN immunoblotting; STROKE volume (Cardiac output); DATA analysis software; PRECIPITIN tests
- Publication
Frontiers in Aging Neuroscience, 2024, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2024.1401038