We have demonstrated that tPA does not play a major role in the etiology of neuroinflammation seen in Cdk5 cKO mice; however, the treatment with pioglitazone significantly reduced the microgliosis, astrogliosis, and neuronal loss and improved the neurological deficit in Cdk5 cKO mice suggesting a beneficial effect of this PPARγ agonist in treating neurodegenerative diseases. Here, CDK5 is linked to neurodegenerative disease.