Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe2+/Cu2+ Chelator in Cell and Animal Models of Parkinson’s Disease
| Autor: | Yorka Muñoz, Victoria Tapia, Bruce K. Cassels, Pabla Aguirre, Olimpo García-Beltrán, Marco T. Núñez |
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| Rok vydání: | 2016 |
| Předmět: |
inorganic chemicals
0301 basic medicine Antioxidant Parkinson's disease Physiology Neurodegeneration with brain iron accumulation Cognitive Neuroscience medicine.medical_treatment Cell Biology General Medicine Mitochondrion medicine.disease Biochemistry Neuroprotection Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Cytoplasm medicine Chelation 030217 neurology & neurosurgery |
| Zdroj: | ACS Chemical Neuroscience. 8:178-185 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.6b00309 |
| Popis: | Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson’s disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ∼ Fe2+ > Zn2+ > Fe3+. No binding capacity was detected for Hg2+, Co2+, Ca2+, Mn2+, Mg2+, Ni2+, Pb2+, or Cd2+. DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY581/591. DHC12 also blocked ... |
| Databáze: | OpenAIRE |
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