The Mitochondrial Cascade Hypothesis for Parkinsons Disease

Sandra      M. Cardoso

Abstract

During the past decades, we have witnessed significant advances in our understanding of the molecular etiology of Parkinsons disease (PD). The unearthing of the causative genes for hereditary PD accelerated not only the studies of the molecular mechanisms underlying this pathology, but also set mitochondria at the center of PD pathology. In this review we revisit mitochondrial key role and propose a hypothesis for PD, that allows the unification of both sporadic and familial PD forms. In light of this we also discuss new promising disease-modified therapies.

Keywords: Mitochondria, mitochondrial DNA, mitochondrial biogenesis, protein oligomerization, intracellular traffic, autophagy, oxidative stress, lysosomal function, Parkinson's Disease, missense mutations