Cashing In with ATM

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Sci. Signal.  06 Jan 2015:
Vol. 8, Issue 358, pp. ec5
DOI: 10.1126/scisignal.aaa5831

Age-related neurodegenerative disorders, including Alzheimer’s disease and Huntington’s disease (HD), consistently show increased markers of DNA damage, which may either be a consequence of or actively contribute to the disease process. Lu et al. showed that ataxia-telangiectasia mutated (ATM), a pivotal signaling molecule in the DNA damage response pathway, altered the toxicity of the mutant protein that causes HD. ATM signaling activity was aberrantly increased in HD cells, animal models of HD, and postmortem brain tissue from HD patients. Reducing ATM signaling by genetic manipulation or using small-molecule inhibitors of ATM consistently reduced toxicities associated with the mutant HD protein in cellular and animal models.

X.-H. Lu, V. B. Mattis, N. Wang, I. Al-Ramahi, N. van den Berg, S. A. Fratantoni, H. Waldvogel, E. Greiner, A. Osmand, K. Elzein, J. Xiao, S. Dijkstra, R. de Pril, H. V. Vinters, R. Faull, E. Signer, S. Kwak, J. J. Marugan, J. Botas, D. F. Fischer, C. N. Svendsen, I. Munoz-Sanjuan, X. W. Yang, Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington’s disease. Sci. Transl. Med. 6, 268ra178 (2014). [Abstract]

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