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Microtubule Depolymerization Potentiates Alpha-Synuclein Oligomerization

Authors
  • Esteves, A. Raquel1
  • Arduíno, Daniela M.1
  • Swerdlow, Russell H.2
  • Oliveira, Catarina R.1, 3
  • Cardoso, Sandra M.1, 3
  • 1 Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Portugal , (Portugal)
  • 2 Departments of Neurology and Molecular and Integrative Physiology, University of Kansas School of Medicine, USA
  • 3 Faculdade de Medicina, Universidade de Coimbra, Portugal , (Portugal)
Type
Published Article
Journal
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Publication Date
Jan 04, 2010
Volume
1
Identifiers
DOI: 10.3389/neuro.24.005.2009
Source
Frontiers
Keywords
Disciplines
  • Neuroscience
  • Original Research
License
Green

Abstract

Parkinson's disease (PD) is associated with perturbed mitochondria function and alpha-synuclein fibrillization. We evaluated potential mechanistic links between mitochondrial dysfunction and alpha-synuclein aggregation. We studied a PD cytoplasmic hybrid (cybrid) cell line in which platelet mitochondria from a PD subject were transferred to NT2 neuronal cells previously depleted of endogenous mitochondrial DNA. Compared to a control cybrid cell line, the PD line showed reduced ATP levels, an increased free/polymerized tubulin ratio, and alpha-synuclein oligomer accumulation. Taxol (which stabilizes microtubules) normalized the PD tubulin ratio and reduced alpha-synuclein oligomerization. A nexus exists between mitochondrial function, cytoskeleton homeostasis, and alpha-synuclein oligomerization. In our model, mitochondrial dysfunction triggers an increased free tubulin, which destabilizes the microtubular network and promotes alpha-synuclein oligomerization.

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