SOD1 and DJ-1 Converge at Nrf2 Pathway: A Clue for Antioxidant Therapeutic Potential in Neurodegeneration

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  • Pamela Milani
    Laboratory of Experimental Neurobiology, National Neurological Institute C. Mondino, IRCCS, Via Mondino 2, 27100 Pavia, Italy
  • Giulia Ambrosi
    Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, National Neurological Institute C. Mondino, IRCCS, Via Mondino 2, 27100 Pavia, Italy
  • Omar Gammoh
    Laboratory of Experimental Neurobiology, National Neurological Institute C. Mondino, IRCCS, Via Mondino 2, 27100 Pavia, Italy
  • Fabio Blandini
    Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, National Neurological Institute C. Mondino, IRCCS, Via Mondino 2, 27100 Pavia, Italy
  • Cristina Cereda
    Laboratory of Experimental Neurobiology, National Neurological Institute C. Mondino, IRCCS, Via Mondino 2, 27100 Pavia, Italy

説明

<jats:p>Neurodegenerative diseases share diverse pathological features and among these oxidative stress (OS) plays a leading role. Impaired activity and reduced expression of antioxidant proteins have been reported as common events in several aging-associated disorders. In this review paper, we first provide an overview of the involvement of reactive oxygen species- (ROS-) induced oxidative damage in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Subsequently, we focus on DJ-1 and SOD1 proteins, which are involved in PD and ALS and also exert a prominent role in the interaction between redox homeostasis and neurodegeneration. Interestingly, recent studies demonstrated that DJ-1 and SOD1 are both tightly connected with Nrf2 protein, a transcriptional factor and master regulator of the expression of many antioxidant/detoxification genes. Nrf2 is emerging as a key neuroprotective protein in neurodegenerative diseases, since it helps neuronal cells to cope with toxic insults and OS. We herein summarize the recent literature providing a detailed picture of the promising therapeutic efficacy of Nrf2 natural and synthetic inducers as disease-modifying molecules for the treatment of neurodegenerative diseases.</jats:p>

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