Roscovitine, a Cyclin-Dependent Kinase-5 Inhibitor, Decreases Phosphorylated Tau Formation and Death of Retinal Ganglion Cells of Rats after Optic Nerve Crush

Tauopathies are neurodegenerative diseases characterized by abnormal metabolism of misfolded tau proteins and progressive. Pathological phosphorylation occurs in the retinal ganglion cells (RGCs) after optic nerve injuries. Cyclin-dependent kinase-5 (Cdk5) causes hyperphosphorylation tau. To determine roles played Cdk5 degeneration, roscovitine, a inhibitor, was injected intravitreally crush (ONC). The neuroprotective effect roscovitine determined number Tuj-1-stained RGCs on day 7. change levels phosphorylated tau, calpain-1, cleaved ?-fodrin immunoblots 3. expression P35/P25, activator, immunohistochemistry. results showed that reduced level 3.5- to 1.6-fold. Calpain-1 (2.1-fold) (1.5-fold) were increased 3, suggesting calpain signaling pathway activated. P35/P25 accumulated poorly stained Tuj-1. Calpain inhibition also increase decreased from 2191 ± 178 (sham) 1216 122 cells/mm2 7, preserved at 1622 130 cells/mm2. We conclude calpain-mediated activation is associated with pathologic