Abstract | BACKGROUND: OBJECTIVE: METHODS/RESULTS: We show by high-performance liquid chromatography, immunohistochemistry and Western blot analyses that the combination of rasagiline and EGCG, at subliminal doses which have no profound protective effect, acts synergistically to restore the nigrostriatal axis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP)-treated mice. A detailed analysis revealed a complementary action of these drugs, differentially acting at MPTP-injured molecules/targets in the substantia nigra (SN): induction of brain-derived neurotrophic factor by rasagiline, increased membranal levels of the protein kinase C alpha- isoform by EGCG and a synergistic replenishment of their downstream effector, the serine/threonine kinase Akt/ protein kinase B, suggesting that this kinase might represent one point of convergence of the distinct mechanisms of action of the drug cocktail. CONCLUSION: These results provide molecular evidence that activation of multiple brain targets by the combination of rasagiline and EGCG may synergistically contribute to the rescue of the dopamine neurons in the SN and replenishment of striatal dopamine. This may have important implications for rasagiline-treated PD patients who could further benefit from an adjunct administration of EGCG.
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Authors | Lydia Reznichenko, Limor Kalfon, Tamar Amit, Moussa B H Youdim, Silvia A Mandel |
Journal | Neuro-degenerative diseases
(Neurodegener Dis)
Vol. 7
Issue 4
Pg. 219-31
( 2010)
ISSN: 1660-2862 [Electronic] Switzerland |
PMID | 20197647
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2010 S. Karger AG, Basel. |
Chemical References |
- Antioxidants
- Drug Combinations
- Indans
- Neuroprotective Agents
- rasagiline
- Catechin
- epigallocatechin gallate
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Topics |
- Animals
- Antioxidants
(pharmacology, therapeutic use)
- Catechin
(analogs & derivatives, pharmacology, therapeutic use)
- Cell Line
- Corpus Striatum
(drug effects, metabolism, physiopathology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Combinations
- Drug Synergism
- Indans
(pharmacology, therapeutic use)
- Male
- Mice
- Mice, Inbred C57BL
- Neural Pathways
(drug effects, metabolism, physiopathology)
- Neuroprotective Agents
(pharmacology, therapeutic use)
- Parkinsonian Disorders
(drug therapy, metabolism, physiopathology)
- Recovery of Function
(drug effects, physiology)
- Substantia Nigra
(drug effects, metabolism, physiopathology)
- Treatment Outcome
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