N-Acetyl-L-Methionyl-L-Dopa-Methyl Ester as a dual acting drug that relieves L-Dopa-induced oxidative toxicity
| Autor: | Ivana Cacciatore, Carmela Conte, Elena Taha, Francesco Pinnen, Catia Cornacchia, Alba Minelli, Elvira Prudenzi |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Antioxidant Parkinson's disease medicine.medical_treatment Apoptosis Oxidative phosphorylation Pharmacology medicine.disease_cause Biochemistry Neuroprotection Antiparkinson Agents Levodopa Mice Mesencephalon Pregnancy Dopamine Physiology (medical) medicine Animals Cells Cultured Neurons Codrug Chemistry Parkinson Disease medicine.disease Glutathione Mice Inbred C57BL Oxidative Stress Animals Newborn Proteasome Cytoprotection Female Heme Oxygenase-1 Oxidative stress medicine.drug |
| Zdroj: | Free Radical Biology and Medicine. 49:31-39 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2010.03.011 |
| Popis: | Initiation and progression of Parkinson's disease seem to be linked to oxidative stress, closely related to decreased mitochondrial functions and ubiquitin proteasome system dysfunction. To date, L-Dopa is the most effective medication , although long-term treatment can enhance oxidative stress and accelerate the degenerative process of residual cells. Therefore the inhibition of oxidation of L-Dopa/dopamine and the inhibition of reactive oxygen species formation are important strategies for neuroprotective therapy. Recently, several dual acting drugs, in which L-Dopa/dopamine are covalently linked to antioxidant molecules, were shown to induce sustained delivery of both L-Dopa/dopamine in rat plasma and striatum, suggesting that these compounds might be proposed as useful agents against Parkinson's disease. Here, by analyzing GSH levels and heme oxygenase-1 expression, we investigated in primary mesencephalic neuron cultures and in newborn mice the effects of the treatment with Ac-Met-LD-OMe. Moreover, by using proteasome inhibitor-treated mice as Parkinson's disease animal model, we demonstrated the beneficial effects of the systemic administration of this novel codrug. |
| Databáze: | OpenAIRE |
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