{Reference Type}: Journal Article
{Title}: Downregulation of Ripk1 and Nsf mediated by CRISPR-CasRx ameliorates stroke volume and neurological deficits after ischemia stroke in mice.
{Author}: Song X;Lan Y;Lv S;Wang Y;Chen L;Lu T;Liu F;Peng D;
{Journal}: Front Aging Neurosci
{Volume}: 16
{Issue}: 0
{Year}: 2024
{Factor}: 5.702
{DOI}: 10.3389/fnagi.2024.1401038
{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.