期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 463, 期 4, 页码 787-792出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.06.014
关键词
Hydroxyquinolines; Iron chelation; Mitochondria; Parkinson's disease
资金
- CONICYT, Chile [3654593]
- FONDECYT [1130068]
- Program of Associative Research [ACT1114]
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. (C) 2015 Elsevier Inc. All rights reserved.
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