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Rasagiline Promotes Regeneration of Substantia Nigra Dopaminergic Neurons in Post-MPTP-induced Parkinsonism via Activation of Tyrosine Kinase Receptor Signaling Pathway.

Authors :
Silvia Mandel
Yotam Sagi
Tamar Amit
Source :
Neurochemical Research; Oct2007, Vol. 32 Issue 10, p1694-1699, 6p
Publication Year :
2007

Abstract

Abstract  The anti-Parkinson drug rasagiline (Azilect), an irreversible and selective monoamine oxidase (MAO)-B inhibitor, was shown to possess neuroprotective activities, involving multiple survival pathways among them the up-regulation of protein kinase C (PKC)α, PKCε, the anti-apoptotic Bcl-2, Bcl-xL, and Bcl-w and the induction of brain-derived- and glial cell line-derived neurotrophic factors (BDNF, GDNF). More recently, employing conventional neurochemical techniques, as well as transcriptomic and proteomic screening tools, combined with a biology-based clustering method, it was shown that rasagiline also possesses neurorescue/neurogenesis activity in mice midbrain dopaminergic neurons when given chronically, post-MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). This action was attributed to the activation of cell signaling mediators associated with neurotrophic factors responsive-tyrosine kinase receptor (Trk) pathway, including ShcC, SOS, AF6, Rin1, and Ras and the increase in the Trk-downstream effecter phosphatidylinositol 3 kinase (PI3K) protein and its substrate, Akt/PKB. It is interesting to determine whether a similar effect is seen in Parkinsonian patients after long-term treatment with rasagiline, which may have implications as a possible disease modifying agent. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03643190
Volume :
32
Issue :
10
Database :
Complementary Index
Journal :
Neurochemical Research
Publication Type :
Academic Journal
Accession number :
26649135
Full Text :
https://doi.org/10.1007/s11064-007-9351-8