Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 20, Issue 35, Pages 5558-5573Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612820666140305224545
Keywords
Parkinson's disease; mitochondrial dysfunction; PGC-1 alpha; sirtuins; creatine; coenzyme-Q10; triterpenoids; bioenergetic defects; neurodegenerative diseases
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Funding
- CSIR Network project [BSC-0115, BSC-0111]
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Parkinson's disease is the second most common neurodegenerative disorder characterized by persistent loss of dopaminergic neurons in the SN and clinically associated with cognitive, behavioral and motor deficits. There is an enormous amount of data that provides convincing evidence about the prime involvement of mitochondria in the onset and progression of neurodegeneration. Several studies have also emphasized that accumulation of toxic protein and their aggregates in mitochondria lead to energy deficits, excessive ROS generation, mutations in mitochondrial genome and proteins regulating mitochondrial homeostasis, and impaired mitochondrial dynamics in animal models of PD and patients. Here we discuss about the bioenergetic agents, which have been tested for reducing the mitochondrial dysfunction and associated disease pathology in cellular and animal models of PD and PD patients with encouraging outcomes. We also provide a succinct overview of current therapeutic implications of PGC-1 alpha, SIRT, AMPK, and Nrf2-ARE as salutary targets to overcome the deleterious effects posed by mitochondrial dysfunction in the onset and progression of PD.
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