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Transcription Modulation of Mitochondrial Function and Related Pathways as a Therapeutic Opportunity in Parkinson’s Disease

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Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease

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Abstract

As outlined in prior chapters, the etiology of Parkinson’s disease (PD) is complex, involving both genetic and environmental factors, necessitating the development of multiple models to study PD. Mounting evidence has established that α-synuclein plays a central role in PD pathogenesis (Brain Pathology 9:707–720, 1999). In α-synucleinopathies, toxic oligomeric forms of α-synuclein may target intracellular organelles and cellular pathways, including mitochondria, the ubiquitin–proteasome system, and the autophagy–lysosome pathway, leading to neuron dysfunction and cell death. In addition, mitochondrial toxins have been identified in epidemiological studies as contributing to “sporadic” PD, and following the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, mitochondrial-based toxin models (paraquat, maneb, rotenone) were developed (Science 219:979–980, 1983; Cell 155:1351–1364, 2013). Mitochondrial dysfunction is thus a common pathological hallmark of PD and may contribute to disease pathogenesis along with altered mitochondrial turnover or reduced mitochondrial biogenesis. Thus, regulators of mitochondrial function are appealing targets for therapeutic strategies to halt or reverse PD neurodegeneration.

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  1. Departments of Cellular & Molecular Medicine, Neurosciences, and Pediatrics, Division of Biological Sciences, The Institute for Genomic Medicine, The Sanford Consortium for Regenerative Medicine, University of California, San Diego, 2880 Torrey Pines Scenic Drive, MC 0642, La Jolla, CA, 92037, USA

    Audrey S. Dickey & Albert R. La Spada M.D., Ph.D.

  2. Rady Children’s Hospital, San Diego, CA, 92123, USA

    Albert R. La Spada M.D., Ph.D.

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  1. Audrey S. Dickey
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    Lori M. Buhlman

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Dickey, A.S., La Spada, A.R. (2016). Transcription Modulation of Mitochondrial Function and Related Pathways as a Therapeutic Opportunity in Parkinson’s Disease. In: Buhlman, L. (eds) Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-42139-1_12

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