The novel mitochondrial iron chelator 5-((methylamino)methyl)-8-hydroxyquinoline protects against mitochondrial-induced oxidative damage and neuronal death
| Autor: | Bruce K. Cassels, Fernanda Lourido, Vicente Castro-Castillo, Pamela J. Urrutia, Olimpo García-Beltrán, Natalia Mena, Marco T. Núñez, Raúl Mena |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Ataxia Parkinson's disease Neurodegeneration with brain iron accumulation Iron Biophysics Substantia nigra Biology Mitochondrion Pharmacology Iron Chelating Agents Biochemistry Mice Oral administration Cell Line Tumor Rotenone medicine Animals Humans Molecular Biology Neurons Cell Death Pars compacta Cell Biology medicine.disease Mitochondria Mice Inbred C57BL Oxidative Stress Cytoplasm Hydroxyquinolines medicine.symptom |
| Zdroj: | Biochemical and Biophysical Research Communications. 463:787-792 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.06.014 |
| Popis: | Abundant evidence indicates that iron accumulation, oxidative damage and mitochondrial dysfunction are common features of Huntington's disease, Parkinson's disease, Friedreich's ataxia and a group of disorders known as Neurodegeneration with Brain Iron Accumulation. In this study, we evaluated the effectiveness of two novel 8-OH-quinoline-based iron chelators, Q1 and Q4, to decrease mitochondrial iron accumulation and oxidative damage in cellular and animal models of PD. We found that at sub-micromolar concentrations, Q1 selectively decreased the mitochondrial iron pool and was extremely effective in protecting against rotenone-induced oxidative damage and death. Q4, in turn, preferentially chelated the cytoplasmic iron pool and presented a decreased capacity to protect against rotenone-induced oxidative damage and death. Oral administration of Q1 to mice protected substantia nigra pars compacta neurons against oxidative damage and MPTP-induced death. Taken together, our results support the concept that oral administration of Q1 is a promising therapeutic strategy for the treatment of NBIA. |
| Databáze: | OpenAIRE |
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