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https://hdl.handle.net/10316/27481
Título: | The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson's disease | Autor: | Esteves, A. R. Gozes, I. Cardoso, S. M. |
Palavras-chave: | NAP; Mitochondria dynamics; Microtubule network | Data: | Jan-2014 | Editora: | Elsevier | Citação: | ESTEVES, A. R.; GOZES, I.; CARDOSO, S. M. - The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson's disease. "Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease". ISSN 0925-4439. Vol. 1842 Nº. 1 (2014) p. 7-21 | Título da revista, periódico, livro ou evento: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | Volume: | 1842 | Número: | 1 | Resumo: | In Parkinson's disease mitochondrial dysfunction can lead to a deficient ATP supply to microtubule protein motors leading to mitochondrial axonal transport disruption. Compromised axonal transport will then lead to a disorganized distribution of mitochondria and other organelles in the cell, as well as, the accumulation of aggregated proteins like alpha-synuclein. Moreover, axonal transport disruption can trigger synaptic accumulation of autophagosomes packed with damaged mitochondria and protein aggregates promoting synaptic failure. We previously observed that neuronal-like cells with an inherent mitochondrial impairment derived from PD patients contain a disorganized microtubule network, as well as, alpha-synuclein oligomer accumulation. In this work we provide new evidence that an agent that promotes microtubule network assembly, NAP (davunetide), improves microtubule-dependent traffic, restores the autophagic flux and potentiates autophagosome–lysosome fusion leading to autophagic vacuole clearance in Parkinson's disease cells. Moreover, NAP is capable of efficiently reducing alpha-synuclein oligomer content and its sequestration by the mitochondria. Most interestingly, NAP decreases mitochondrial ubiquitination levels, as well as, increases mitochondrial membrane potential indicating a rescue in mitochondrial function. Overall, we demonstrate that by improving microtubule-mediated traffic, we can avoid mitochondrial-induced damage and thus recover cell homeostasis. These results prove that NAP may be a promising therapeutic lead candidate for neurodegenerative diseases that involve axonal transport failure and mitochondrial impairment as hallmarks, like Parkinson's disease and related disorders. | URI: | https://hdl.handle.net/10316/27481 | ISSN: | 0925-4439 | DOI: | 10.1016/j.bbadis.2013.10.003 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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The rescue of microtubule-dependent traffic recovers mitochondrial function.pdf | 709.26 kB | Adobe PDF | Ver/Abrir |
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