Abstract:
:Parkinson's disease (PD) is a neurodegenerative disorder characterised by selective degeneration of the nigral dopaminergic neurons, and neuroinflammation and oxidative stress are believed to be involved in its pathogenesis. In the present study, we provide data that the synthetic steroid exemestane, which is currently being used to treat breast cancer, may be useful for PD therapy. In BV-2 microglial cells, exemestane activated the transcription factor Nrf2 and induced expression of the Nrf2-dependent genes that encode the antioxidant enzymes NAD(P)H: quinone oxidoreductase 1, haem oxygenase-1, and glutamylcysteine ligase. It also downregulated gene expression of inducible nitric oxide (NO) synthase, lowered the levels of NO and reactive oxygen species, interleukin-1β and tumour necrosis factor-α in lipopolysaccharide-activated microglial cells. In CATH.a dopaminergic neuronal cells, exemestane also induced the same set of Nrf2-dependent antioxidant enzyme genes and provided neuroprotection against oxidative damage. In vivo, the drug protected the nigral dopaminergic neurons, decreased microglial activation, and prevented motor deficits in C57Bl/6 male mice that had been administered with the dopaminergic neurotoxin MPTP. Taken together, the results suggested a utility of repositioning exemestane towards disease-modifying therapy for PD.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Son HJ,Han SH,Lee JA,Shin EJ,Hwang Odoi
10.1080/10715762.2017.1353688subject
Has Abstractpub_date
2017-06-01 00:00:00pages
633-645issue
6eissn
1071-5762issn
1029-2470journal_volume
51pub_type
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