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Nrf2/ARE Pathway as a Therapeutic Target for the Treatment of Parkinson Diseases

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Abstract

Instead of the progress in the understanding of etiology of Parkinson’s disease (PD), effective methods to prevent the progression of the disease have not been developed and only symptomatic treatment is currently possible. One of possible pathways to slow the progression of the disease is protection of dopaminergic neurons by maintaining mitochondrial quality control in neuron cells. Recent studies showed that the most promising target for pharmacological effects on mitochondria is the Nrf2/ARE signaling cascade. It participates in the maintenance of mitochondrial homeostasis, which is provided by an optimal ratio in the processes of mitochondrial biogenesis and mitophagy, as well as the optimal ratio of ROS production and ROS scavenging. Nrf2 activators are capable of modulating these processes, maintaining mitochondrial homeostasis in neurons. In addition, Nrf2 can synergistically interact with other transcription factors, for example, PGC-1a in the regulation of mitochondrial biogenesis and YY1 with the increase of antioxidant defense. All this makes Nrf2 an optimal target for drugs that could support the mitochondrial quality control, which, in combination with antioxidant protection, can significantly slow down the pathogenesis of PD. Some of these compounds have undergone laboratory studies and are at the stage of clinical trials now.

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Acknowledgements

This research was supported by the Ministry of Education and Science of the Russian Federation (State Assessment N 6.4656.2017/8.9); President grant for support of leading scientific school, (Agreement 14.Z57.18.3451-NSh) and Russian Fund for Basic Research (16-04-01014 А).

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    Artem P. Gureev & Vasily N. Popov

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Gureev, A.P., Popov, V.N. Nrf2/ARE Pathway as a Therapeutic Target for the Treatment of Parkinson Diseases. Neurochem Res 44, 2273–2279 (2019). https://doi.org/10.1007/s11064-018-02711-2

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