Article ID Journal Published Year Pages File Type
2030583 Trends in Biochemical Sciences 2015 11 Pages PDF
Abstract

•A number of biochemical perturbations in Parkinson's disease (PD) are linked to mitochondrial dysfunction.•Progress in 2014 has defined new mechanisms of PINK1 and parkin-dependent mitophagy.•α-Synuclein (α-syn) levels and aggregation link mitochondria to familial and sporadic PD.•These new insights suggest novel mechanisms and therapeutic targets in PD.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by the preferential loss of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuronal susceptibility in PD and is a feature of both familial and sporadic disease, as well as in toxin-induced Parkinsonism. Recently, the mechanisms by which PD-associated mitochondrial proteins phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1) and parkin function and induce neurodegeneration have been identified. In addition, increasing evidence implicates other PD-associated proteins such as α-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) in mitochondrial dysfunction in genetic cases of PD with the potential for a large functional overlap with sporadic disease. This review highlights how recent advances in understanding familial PD-associated proteins have identified novel mechanisms and therapeutic strategies for addressing mitochondrial dysfunction in PD.

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