Microtubule depolymerization potentiates alpha-synuclein oligomerization

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 mit...

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Published inFrontiers in aging neuroscience Vol. 1; p. 5
Main Author Esteves, A. Raquel
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 04.01.2010
Frontiers Media S.A
Subjects
alpha-Synuclein
ATP
Blood platelets
cybrids
Cytoskeleton
Deoxyribonucleic acid
Depolymerization
DNA
Experiments
Fibrillogenesis
Homeostasis
Human subjects
Microtubules
Mitochondria
Mitochondrial DNA
Movement disorders
Mutation
Neurodegenerative diseases
Neuroscience
Neurotrophin 2
Oligomerization
Oxidative stress
Paclitaxel
Parkinson Disease
Parkinson's disease
Penicillin
Synuclein
Tubulin
United States > US
Portugal
Parkinson disease
tubulin
alpha-synuclein
ATP
mitochondria
cybrids
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Summary: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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Edited by: Paula I. Moreira, University of Coimbra, Portugal
Reviewed by: George Perry, The University of Texas at San Antonio, USA; Akihiko Nunomura, University of Yamanashi, Japan
ISSN:1663-4365
1663-4365
DOI:10.3389/neuro.24.005.2009