Regulation of protein kinase C by the anti‐Parkinson drug, MAO‐B inhibitor, rasagiline and its derivatives, in vivo

• DOI: 10.1111/j.1471-4159.2004.02425.x
• Publication Date: 2004-05-14T15:46:52Z
• Authors: Orit Bar‐Am; Merav Yogev‐Falach; Tamar Amit; Yotam Sagi; Moussa B. H. Youdim
• Keywords: Rasagiline; MARCKS

Abstract We have recently shown that the anti‐Parkinson‐propargyl‐containing monoamine oxidase B (MAO‐B) inhibitor drug, rasagiline [ N ‐propargyl‐(1R)‐aminoindan], and its cholinesterase derivatives TV3326 TV3279, regulate amyloid precursor protein (APP) processing by a kinase C (PKC)‐dependent mechanism in SH‐SY5Y neuroblastoma PC12 cells. In present study, we investigated effect of on regulation PKC‐dependent APP under vivo conditions. Administration (0.1 mg/kg) to male C57/BL mice for 14 days significantly decreased membrane‐bound holoprotein levels hippocampus. Additionally, observed up‐regulated p‐PKC expression α ε PKC isozymes hippocampus, indicating which affects may be related PKC‐associated signalling. The results also demonstrate treatment elevated phosphorylated myristoylated alanine‐rich substrate (p‐MARCKS), major PKC, as well receptors activated 1 (RACK1). Similar effects were demonstrated two rasagiline, TV3279. These indicate mechanisms processing. activation induction MARCKS these drugs crucial role not only their neuroprotective activity, but ability affect neuronal plasticity spatial learning processes.