Activation of nuclear factor erythroid 2-related factor 2 cytoprotective signaling by curcumin protect primary spinal cord astrocytes against oxidative toxicity

Abstract

Oxidative damage plays a critical role in many neurodegenerative diseases. Astrocytes are involved in supporting the survival and protection of neurons against oxidative damage. The dysfunction of antioxidant in astrocytes has been implicated in a variety of neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), spinalmuscularatrophy (SMA). The loss of motor neuron in spinal cord has been attributed to deterioration of astrocytes. The activation of antioxidantive function in astrocytes may serve as a therapeutic strategy for neurodegenerative diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional regulator of phase II antioxidantive genes. We report herein that curcumin significantly activates Nrf2 target genes in primary spinal cord astrocytes, decreases the level of intracellular reactive oxygen species (ROS), and attenuates oxidative damage and mitochondrial dysfunction. © 2011 Pharmaceutical Society of Japan.