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Trends Biochem Sci. 2015 Apr;40(4):200-10. doi: 10.1016/j.tibs.2015.02.003. Epub 2015 Mar 8.

Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease.

Author information

1
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.
2
McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec H3A 2B4, Canada.
3
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.

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.

KEYWORDS:

Parkinson's disease; mitochondrial dysfunction; mitophagy; oxidative stress; α-synuclein

PMID:
25757399
DOI:
10.1016/j.tibs.2015.02.003
[Indexed for MEDLINE]

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