%0 Journal Article %1 RN243 %A Mena, N.P. %A Garcia-Beltran, O. %A Lourido, F. %A Urrutia, P.J. %A Mena, R. %A Castro-Castillo, V. %A Cassels, B.K. %A Nunez, M.T. %D 2015 %I 2015 Elsevier Inc. %J Biochemical and Biophysical Research Communications %K accumulation, brain chelation, contributes, degeneration, disease, diseases, dqcauchile homeostasis, hydroxyquinolines, in-vivo, inhibition iron iron, mitochondria, neurodegenerative parkinson's parkinsons-disease, substantia-nigra, %N 4 %P 787-792 %R 10.1016/j.bbrc.2015.06.014 %T The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death %U /brokenurl#<Go to ISI>://WOS:000358455300051 %V 463 %X 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.

@article{RN243, abstract = {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. }, added-at = {2019-12-04T03:57:35.000+0100}, author = {Mena, N.P. and Garcia-Beltran, O. and Lourido, F. and Urrutia, P.J. and Mena, R. and Castro-Castillo, V. and Cassels, B.K. and Nunez, M.T.}, biburl = {https://www.bibsonomy.org/bibtex/27f23651cf4f4d50056cfd32d10c34f78/dqcauchile}, doi = {10.1016/j.bbrc.2015.06.014}, interhash = {7c4031aec38f7347bba830ef1bfe9fca}, intrahash = {7f23651cf4f4d50056cfd32d10c34f78}, issn = {0006-291x}, journal = {Biochemical and Biophysical Research Communications}, keywords = {accumulation, brain chelation, contributes, degeneration, disease, diseases, dqcauchile homeostasis, hydroxyquinolines, in-vivo, inhibition iron iron, mitochondria, neurodegenerative parkinson's parkinsons-disease, substantia-nigra,}, number = 4, pages = {787-792}, publisher = {2015 Elsevier Inc.}, timestamp = {2019-12-04T03:58:17.000+0100}, title = {The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death}, type = {Journal Article}, url = {/brokenurl#<Go to ISI>://WOS:000358455300051}, volume = 463, year = 2015 }