Cdk5 and Nuclear Fragmentation in AD

Cdk5 is considered to be neuroprotective in the cytoplasm, and neurotoxic in the nucleus. Our studies have demonstrated that b-amyloid treatment or excitotoxicity deregulates Cdk5 in primary cortical neurons, which phosphorylates nuclear proteins Lamin A and Lamin B1 proteins causing rapid nuclear dispersion. Nuclear dispersion allows Cdk5 to mislocalize in the nucleus, where it triggers the activation of several pro-apoptotic genes leading to neurodegeneration.