Research Paper Volume 13, Issue 5 pp 6634—6661

CRISPR/Cas9-mediated CysLT1R deletion reverses synaptic failure, amyloidosis and cognitive impairment in APP/PS1 mice

The proposed mechanism for CysLT1R-mediated AD pathology. Aβ accumulation upregulates Cys-LTs inducing CysLT1R expression, which activates NF-κB pathway followed by increased release of proinflammatory cytokines. Consequently, proinflammatory cytokines induce neuronal apoptosis and KP dysregulation with increased expression of IDO and KYUN and the synthesis of QUIN. Moreover, neuroinflammation accelerates amyloid deposition, forming a vicious circle. This leads to NMDARs overactivation and excitotoxicity correlated with synaptic dysfunction and cognitive deficits.

Figure 7. The proposed mechanism for CysLT1R-mediated AD pathology. Aβ accumulation upregulates Cys-LTs inducing CysLT1R expression, which activates NF-κB pathway followed by increased release of proinflammatory cytokines. Consequently, proinflammatory cytokines induce neuronal apoptosis and KP dysregulation with increased expression of IDO and KYUN and the synthesis of QUIN. Moreover, neuroinflammation accelerates amyloid deposition, forming a vicious circle. This leads to NMDARs overactivation and excitotoxicity correlated with synaptic dysfunction and cognitive deficits.