Wednesday, January 30, 2019

Study of neuroprotection by urate using fly model of ALS

Zhang C, Yang Y, Liang W, Wang T, Wang S, Wang X, Wang Y, Jiang H, Feng H. Neuroprotection by urate on the Mutant hSOD1-related Cellular and Drosophila Models of Amyotrophic Lateral Sclerosis: Implication for GSH synthesis via Activating Akt/GSK3β/Nrf2/GCLC Pathways. Brain Res Bull. 2019 Jan 25. pii: S0361-9230(18)30605-1. PMID: 30690059.

From the abstract
: "Oxidative stress has been considered as a principal mechanism of motor neuron death in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease which could be caused by dominant mutations in an antioxidant enzyme superoxide dismutase-1 (SOD1). The aim of the present study was to investigate the potential neuroprotective effects and mechanisms of urate, an important endogenous antioxidant and a biomarker of favorable ALS progression rates, in the mutant human SOD1-related cellular and Drosophila models of ALS. Our results showed that urate treatment provided neuroprotective effects as confirmed by enhanced survival, attenuated motor impairments, reduced oxidative damage and increased antioxidant defense in hSOD1-G85R-expressing Drosophila models of ALS. ... Overall, these results suggested that, in addition to its direct scavenging of ROS, urate markedly enhanced GSH expression by activating Akt/GSK3β/Nrf2/GCLC pathway, and thus offering neuroprotective effects on motor neurons against oxidative stress."

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