2015 |
Aguirre, P; Mena, N P; Carrasco, C M; Munoz, Y; Perez-Henriquez, P; Morales, R A; Cassels, B K; Mendez-Galvez, C; Garcia-Beltran, O; González-Billault, C; Nunez, M Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons Artículo de revista Plos One, 10 (12), 2015, ISSN: 1932-6203. Resumen | Enlaces | BibTeX | Etiquetas: apoptosis, degeneration, dendritic disease, expression, induced models, neurodegeneration, protein, restoration substantia-nigra, tree @article{RN242, title = {Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons}, author = { P. Aguirre and N.P. Mena and C.M. Carrasco and Y. Munoz and P. Perez-Henriquez and R.A. Morales and B.K. Cassels and C. Mendez-Galvez and O. Garcia-Beltran and C. Gonz\'{a}lez-Billault and M. Nunez}, url = {/brokenurl#<Go to ISI>://WOS:000366715900118}, doi = {10.1371/journal.pone.0144848}, issn = {1932-6203}, year = {2015}, date = {2015-01-01}, journal = {Plos One}, volume = {10}, number = {12}, abstract = {Neuronal death in Parkinson's disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.}, keywords = {apoptosis, degeneration, dendritic disease, expression, induced models, neurodegeneration, protein, restoration substantia-nigra, tree}, pubstate = {published}, tppubtype = {article} } Neuronal death in Parkinson's disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death. |
Mena, N P; Garcia-Beltran, O; Lourido, F; Urrutia, P J; Mena, R; Castro-Castillo, V; Cassels, B K; Nunez, M The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death Artículo de revista Biochemical and Biophysical Research Communications, 463 (4), pp. 787-792, 2015, ISSN: 0006-291x. Resumen | Enlaces | BibTeX | Etiquetas: brain chelation, contributes, degeneration, disease, diseases, homeostasis, hydroxyquinolines, in-vivo, inhibition iron iron, mitochondria, neurodegenerative parkinson's parkinsons-disease, substantia-nigra @article{RN243, title = {The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death}, author = { N.P. Mena and O. Garcia-Beltran and F. Lourido and P.J. Urrutia and R. Mena and V. Castro-Castillo and B.K. Cassels and M. Nunez}, url = {/brokenurl#<Go to ISI>://WOS:000358455300051}, doi = {10.1016/j.bbrc.2015.06.014}, issn = {0006-291x}, year = {2015}, date = {2015-01-01}, journal = {Biochemical and Biophysical Research Communications}, volume = {463}, number = {4}, pages = {787-792}, publisher = {2015 Elsevier Inc.}, 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.}, keywords = {brain chelation, contributes, degeneration, disease, diseases, homeostasis, hydroxyquinolines, in-vivo, inhibition iron iron, mitochondria, neurodegenerative parkinson's parkinsons-disease, substantia-nigra}, pubstate = {published}, tppubtype = {article} } 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. |
2015 |
Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons Artículo de revista Plos One, 10 (12), 2015, ISSN: 1932-6203. |
The Novel Mitochondrial Iron Chelator 5-((Methylamino)Methyl)-8-Hydroxyquinoline Protects against Mitochondrial-Induced Oxidative Damage and Neuronal Death Artículo de revista Biochemical and Biophysical Research Communications, 463 (4), pp. 787-792, 2015, ISSN: 0006-291x. |