title: Microtubule depolymerization potentiates alpha-synuclein oligomerization.
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.
authors.affiliation: Centro de Neurociências e Biologia Celular, Universidade de Coimbra Portugal.
authors.forename: A Raquel
authors.initials: AR
authors.lastname: Esteves
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Arduíno
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Cardoso