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Abstract
<p class="first" id="d5175404e86">New discoveries providing insights into mitochondrial
bioenergetics, their dynamic
interactions as well as their role in cellular homeostasis have dramatically advanced
our understanding of the neurodegenerative process of Parkinson's disease (PD). Respiratory
chain impairment is a key feature in sporadic PD patients and there is growing evidence
that links proteins encoded by PD-associated genes to disturbances in mitochondrial
function. Against the backdrop of latest advances in the development of PD treatments
that target mitochondria, we aim to give an overview of the literature published in
the last three decades on the significance of mitochondria in the pathogenesis of
PD. We describe the contribution of mitochondrial genome alterations and PD-associated
genes to mitochondrial maintenance. We highlight mitophagy as a key mechanism in neurodegeneration.
Moreover, we focus on the reciprocal interaction between alpha-synuclein aggregation
and mitochondrial dysfunction. We discuss a novel trafficking pathway involving mitochondrial-derived
vesicles within the context of PD and provide a synopsis of the most recently emerging
topics in PD research with respect to mitochondria. This includes the relationship
between mitochondria and cell-mediated immunity, the ER-mitochondria axis, sirtuin-mediated
mitochondrial stress response and the role of micro RNAs in the aetiology of PD. In
addition, recent studies have challenged the neuro-centric view of PD pathology, moving
microglia and astrocytes into the research spotlight. Greater insights into these
mechanisms may hold the key for the development of novel targeted therapies, addressing
the need for a disease-modifying treatment, which has remained elusive to date.
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