DOI: 10.1111/j.1471-4159.2004.02425.x. Regulation of protein kinase C by the anti‐Parkinson drug, MAO‐B inhibitor, rasagiline and its derivatives, <i>in vivo</i>

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

10.1111/j.1471-4159.2004.02425.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

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

Bibliography

BarâAm, O., YogevâFalach, M., Amit, T., Sagi, Y., & Youdim, M. B. H. (2004). Regulation of protein kinase C by the antiâParkinson drug, MAOâB inhibitor, rasagiline and its derivatives, in vivo. Journal of Neurochemistry, 89(5), 1119â1125. Portico.

Authors 5

Orit Bar‐Am (first)
Merav Yogev‐Falach (additional)
Tamar Amit (additional)
Yotam Sagi (additional)
Moussa B. H. Youdim (additional)

References 55 Referenced 89

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Dates

Type	When
Created	21 years, 3 months ago (May 14, 2004, 11:46 a.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 4:44 p.m.)
Indexed	45 minutes ago (Sept. 2, 2025, 10:03 p.m.)
Issued	21 years, 4 months ago (April 26, 2004)
Published	21 years, 4 months ago (April 26, 2004)
Published Online	21 years, 4 months ago (April 26, 2004)
Published Print	21 years, 3 months ago (June 1, 2004)

Funders 0

None

BibTeX

@article{Bar_Am_2004, title={Regulation of protein kinase C by the anti‐Parkinson drug, MAO‐B inhibitor, rasagiline and its derivatives, in vivo}, volume={89}, ISSN={1471-4159}, url={http://dx.doi.org/10.1111/j.1471-4159.2004.02425.x}, DOI={10.1111/j.1471-4159.2004.02425.x}, number={5}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Bar‐Am, Orit and Yogev‐Falach, Merav and Amit, Tamar and Sagi, Yotam and Youdim, Moussa B. H.}, year={2004}, month=apr, pages={1119–1125} }

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