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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.
- 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]
- Subjects :
- SUBSTANTIA nigra
DOPAMINERGIC neurons
PARKINSON'S disease
PROTEIN-tyrosine kinases
Subjects
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