The Effect Of Cyclin Dependent Kinase-5 On Neurodeneration In Niemann-Pick Type C

Objective: To determine precise role of cdk5 in NPC neurodegeneration in order to develop method to treat the neurodegenerative disease.Methods: To construct the adeno_associated virus vector encoding the small interfering RNA( siRNA) specific for cyclin dependent kinase₅ (cdk₅) gene.4_weeks mice were injected with rAAV_cdk5_siRNA_GFP and rAAV_GFP respectively. After 4 weeks the activity of cdk5 in the mice's cerebellar was detected whether it decrease or not and the change of the mice ethology,neuropathology and biochemistry were observed too.Results: rAAV_cdk5_siRNA_GFP can reduce significantly the expression of cdk5 gene ,ameliorated motor defects in npc mice, reduced the number of axonal spheroids, delayed the death of Purkinje neuron,and attenuated significantly the hyperphosphorylation of tau proteins.Conclusions: cdk5 plays essential role in the neurodegenerative process of NPC.