Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels

Chisato Kinoshita, Koji Aoyama, Nobuko Matsumura, Kazue Kikuchi-Utsumi, Masahiko Watabe and Toshio Nakaki ()
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Chisato Kinoshita: Teikyo University School of Medicine
Koji Aoyama: Teikyo University School of Medicine
Nobuko Matsumura: Teikyo University School of Medicine
Kazue Kikuchi-Utsumi: Teikyo University School of Medicine
Masahiko Watabe: Teikyo University School of Medicine
Toshio Nakaki: Teikyo University School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Glutathione (GSH) is a key antioxidant that plays an important neuroprotective role in the brain. Decreased GSH levels are associated with neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Here we show that a diurnal fluctuation of GSH levels is correlated with neuroprotective activity against oxidative stress in dopaminergic cells. In addition, we found that the cysteine transporter excitatory amino acid carrier 1 (EAAC1), which is involved in neuronal GSH synthesis, is negatively regulated by the microRNA miR-96-5p, which exhibits a diurnal rhythm. Blocking miR-96-5p by intracerebroventricular administration of an inhibitor increased the level of EAAC1 as well as that of GSH and had a neuroprotective effect against oxidative stress in the mouse substantia nigra. Our results suggest that the diurnal rhythm of miR-96-5p may play a role in neuroprotection by regulating neuronal GSH levels via EAAC1.

Date: 2014
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DOI: 10.1038/ncomms4823

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