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Roscovitine, a Cyclin-Dependent Kinase-5 Inhibitor, Decreases Phosphorylated Tau Formation and Death of Retinal Ganglion Cells of Rats after Optic Nerve Crush
| Content Provider | MDPI |
|---|---|
| Author | Hirokawa, Takahisa Horie, Taeko Fukiyama, Yurie Mimura, Masashi Takai, Shinji Kida, Teruyo Oku, Hidehiro |
| Copyright Year | 2021 |
| Description | Tauopathies are neurodegenerative diseases characterized by abnormal metabolism of misfolded tau proteins and are progressive. Pathological phosphorylation of tau occurs in the retinal ganglion cells (RGCs) after optic nerve injuries. Cyclin-dependent kinase-5 (Cdk5) causes hyperphosphorylation of tau. To determine the roles played by Cdk5 in retinal degeneration, roscovitine, a Cdk5 inhibitor, was injected intravitreally after optic nerve crush (ONC). The neuroprotective effect of roscovitine was determined by the number of Tuj-1-stained RGCs on day 7. The change in the levels of phosphorylated tau, calpain-1, and cleaved α-fodrin was determined by immunoblots on day 3. The expression of P35/P25, a Cdk5 activator, in the RGCs was determined by immunohistochemistry. The results showed that roscovitine reduced the level of phosphorylated tau by 3.5- to 1.6-fold. Calpain-1 (2.1-fold) and cleaved α-fodrin (1.5-fold) were increased on day 3, suggesting that the calpain signaling pathway was activated. P35/P25 was accumulated in the RGCs that were poorly stained by Tuj-1. Calpain inhibition also reduced the increase in phosphorylated tau. The number of RGCs decreased from 2191 ± 178 (sham) to 1216 ± 122 $cells/mm^{2}$ on day 7, and roscovitine preserved the level at 1622 ± 130 $cells/mm^{2}$. We conclude that the calpain-mediated activation of Cdk5 is associated with the pathologic phosphorylation of tau. |
| Starting Page | 8096 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms22158096 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 15 |
| Volume Number | 22 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-07-28 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Pathology Tauopathy Cyclin-dependent Kinase 5 (cdk5) Roscovitine Calpain Optic Nerve Crush |
| Content Type | Text |
| Resource Type | Article |
