title: Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD.
abstract: While the etiology of Parkinson's disease remains largely elusive, there is accumulating evidence suggesting that mitochondrial dysfunction occurs prior to the onset of symptoms in Parkinson's disease. Mitochondria are remarkably primed to play a vital role in neuronal cell survival since they are key regulators of energy metabolism (as ATP producers), of intracellular calcium homeostasis, of NAD(+)/NADH ratio, and of endogenous reactive oxygen species production and programmed cell death. In this paper, we focus on mitochondrial dysfunction-mediated alpha-synuclein aggregation. We highlight some of the findings that provide proof of evidence for a mitochondrial metabolism control in Parkinson's disease, namely, mitochondrial regulation of microtubule-dependent cellular traffic and autophagic lysosomal pathway. The knowledge that microtubule alterations may lead to autophagic deficiency and may compromise the cellular degradation mechanisms that culminate in the progressive accumulation of aberrant protein aggregates shields new insights to the way we address Parkinson's disease. In line with this knowledge, an innovative window for new therapeutic strategies aimed to restore microtubule network may be unlocked.
authors.affiliation: Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004 Coimbra, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Esteves
authors.forename: D M
authors.initials: DM
authors.lastname: Arduíno
authors.forename: D F F
authors.initials: DF
authors.lastname: Silva
authors.forename: C R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: S M
authors.initials: SM
authors.lastname: Cardoso