title: Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease.
abstract: 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.
authors.affiliation: Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Ryan
authors.affiliation: Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
authors.forename: Selim
authors.initials: S
authors.lastname: Hoek
authors.affiliation: McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fon
authors.affiliation: Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK. Electronic address: richard.wade-martins@dpag.ox.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Wade-Martins
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein
keywords: Parkinson's disease; mitochondrial dysfunction; mitophagy; oxidative stress; α-synuclein