Identification of a molecular network of DNA damage-induced neural cell death

DNA damage plays a major role in neural cell death by necrosis and/or apoptosis. However, our understanding of the molecular mechanisms of neural cell death remains still incomplete. To acquire a global understanding of the various mediators related to DNA damage-induced neural cell death pathways, we performed a whole genomic wide screen in neural stem cells by using a siRNA library. We identified 80 genes required for DNA damage-induced cell death. 14 genes (17.5%) are directly related to cell death and/or apoptosis. 66 genes have not been previously directly linked to DNA damage-induced cell death. Using an integrated approach with functional and bioinformatics analysis, we have uncovered a molecular network containing several partially overlapping and interconnected pathways and/or protein complexes that are required for DNA damage-induced neural cell death. The identification of the network of neural cell death mediators will greatly enhance our understanding of the molecular mechanisms of neural cell death and provide therapeutic targets for nervous system disorders.

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Zhang J, Wang H, Sherbini O, Ling-Lin Pai E, Kang SU, Kwon JS, Yang J, He W, Wang H, Eacker SM, Chi Z, Mao X, Xu J, Jiang H, Andrabi SA, Dawson TM, Dawson VL