Sustained stimulation of the NLRP3 inflammasome causes inflammation in the absence of GSDMD.

We show that nuclear fragmentation in neurodegeneration is an early trigger for cell death initiated by deregulated Cdk5. Cdk5 induces nuclear dispersion by direct phosphorylation of lamins in neurons and in vivo Alzheimer's disease (AD) mouse models. Inhibition of nuclear fragmentation rescues neurons from cell death, underscoring the significance of this event in AD.