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Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons.
Reeve, A K; Ludtmann, M H R; Angelova, P R; Simcox, E M; Horrocks, M H; Klenerman, D; Gandhi, S; Turnbull, D M; Abramov, A Y.
Affiliation
  • Reeve AK; Wellcome Trust Centre for Mitochondrial Research, Institute for Neuroscience, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK.
  • Ludtmann MH; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
  • Angelova PR; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
  • Simcox EM; Wellcome Trust Centre for Mitochondrial Research, Institute for Neuroscience, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK.
  • Horrocks MH; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
  • Klenerman D; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
  • Gandhi S; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
  • Turnbull DM; Wellcome Trust Centre for Mitochondrial Research, Institute for Neuroscience, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK.
  • Abramov AY; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
Cell Death Dis ; 6: e1820, 2015 Jul 16.
Article in En | MEDLINE | ID: mdl-26181201
α-Synuclein becomes misfolded and aggregated upon damage by various factors, for example, by reactive oxygen species. These aggregated forms have been proposed to have differential toxicities and their interaction with mitochondria may cause dysfunction within this organelle that contributes to the pathogenesis of Parkinson's disease (PD). In particular, the association of α-synuclein with mitochondria occurs through interaction with mitochondrial complex I and importantly defects of this protein have been linked to the pathogenesis of PD. Therefore, we investigated the relationship between aggregated α-synuclein and mitochondrial dysfunction, and the consequences of this interaction on cell survival. To do this, we studied the effects of α-synuclein on cybrid cell lines harbouring mutations in either mitochondrial complex I or IV. We found that aggregated α-synuclein inhibited mitochondrial complex I in control and complex IV-deficient cells. However, when aggregated α-synuclein was applied to complex I-deficient cells, there was no additional inhibition of mitochondrial function or increase in cell death. This would suggest that as complex I-deficient cells have already adapted to their mitochondrial defect, the subsequent toxic effects of α-synuclein are reduced.
Subject(s)

Full text: 1 Collection: 01-internacional Health context: 6_ODS3_enfermedades_notrasmisibles Database: MEDLINE Main subject: Parkinson Disease / Oxidative Stress / Alpha-Synuclein / Neurons Limits: Animals / Humans Language: En Journal: Cell Death Dis Year: 2015 Document type: Article

Full text: 1 Collection: 01-internacional Health context: 6_ODS3_enfermedades_notrasmisibles Database: MEDLINE Main subject: Parkinson Disease / Oxidative Stress / Alpha-Synuclein / Neurons Limits: Animals / Humans Language: En Journal: Cell Death Dis Year: 2015 Document type: Article