The neuroprotective effects of cyclin-dependent kinase-5 inhibition in mice with Niemann-Pick disease type C
Copyright policy )The neuroprotective effects of cyclin-dependent kinase-5 inhibition in mice with Niemann-Pick disease type C
In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc(-/-)), recombinant adeno-associated virus (rAAV) carrying the small interfering RNA (siRNA) specific for cdk-5 gene was injected into 3-day-old npc(-/-) mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc(-/-) mice and non-surgery age-matched npc(-/-) mice were employed as controls (n=6-10/group). From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc(-/-) mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc(-/-) mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc(-/-) mice, and significantly attenuated the hyperphosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice.
- Huazhong University of Science and Technology China (People's Republic of)
- Tongji Hospital China (People's Republic of)
Niemann-Pick Diseases, Mice, Inbred BALB C, Gene Transfer Techniques, Intracellular Signaling Peptides and Proteins, Proteins, Cyclin-Dependent Kinase 5, tau Proteins, Genetic Therapy, Dependovirus, Mice, Mice, Neurologic Mutants, Purkinje Cells, Niemann-Pick C1 Protein, Animals, Phosphorylation, RNA, Small Interfering
Niemann-Pick Diseases, Mice, Inbred BALB C, Gene Transfer Techniques, Intracellular Signaling Peptides and Proteins, Proteins, Cyclin-Dependent Kinase 5, tau Proteins, Genetic Therapy, Dependovirus, Mice, Mice, Neurologic Mutants, Purkinje Cells, Niemann-Pick C1 Protein, Animals, Phosphorylation, RNA, Small Interfering
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