The high-affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA-induced apoptotic cell death and rescues dopaminergic neurons in the MPTP mouse model of Parkinson's disease
| Autor: | Chandrashekhar Voshavar, Julie K. Andersen, Mrudang M. Shah, Liping Xu, Subramanian Rajagopalan, Aloke K. Dutta, Yevgeniya I. Shurubor, Flint Beal |
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| Rok vydání: | 2013 |
| Předmět: |
Agonist
Male Parkinson's disease Indoles medicine.drug_class Substantia nigra Apoptosis Pharmacology Biology medicine.disease_cause Biochemistry Neuroprotection PC12 Cells Article Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Parkinsonian Disorders medicine Animals Oxidopamine Cell Death Dose-Response Relationship Drug Receptors Dopamine D2 MPTP Dopaminergic Neurons Dopaminergic Receptors Dopamine D3 medicine.disease Rats Mice Inbred C57BL Thiazoles chemistry nervous system Systemic administration Reactive Oxygen Species Oxidative stress |
| Zdroj: | Journal of neurochemistry. 131(1) |
| ISSN: | 1471-4159 |
| Popis: | In this study, in vitro and in vivo experiments were carried out with the high-affinity multifunctional D2/D3 agonist D-512 in order to explore its potential neuroprotective effects in models of Parkinson’s disease (PD) and the potential mechanism(s) underlying such properties. Pretreatment with D-512 in vitro was found to rescue rat adrenal phaeochromocytoma PC12 cells from toxicity induced by 6-hydroxydopamine (6-OHDA) administration in a dose-dependent manner. Neuroprotection was found to coincide with reductions in intracellular reactive oxygen species, lipid peroxidation, and DNA damage. In vivo, pretreatment with 0.5 mg/kg D-512 was protective against neurodegenerative phenotypes associated with systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), including losses in striatal dopamine (DA), reductions in numbers of DAergic neurons in the substantia nigra (SN), and locomotor dysfunction. These observations strongly suggest that the multifunctional drug D-512 may constitute a novel viable therapy for PD. |
| Databáze: | OpenAIRE |
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