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. 2015 Dec 17;25(6):1043–1058. doi: 10.1093/hmg/ddv513

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© The Author 2015. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Figure 5. — AMPK has a protective function in and in vitro model of HD. (A) Growing striatal cells in metformin 2 mm reduces mortality induced by serum deprivation in 109Q/109Q mouse striatal cells (***P < 0.001, N = 3). The right panel shows representative western blots to show that AMPKγ1GOF induces phosphorylation of AMPKα in striatal cells. The levels of Htt do not change. (B) Silencing AMPKα1 by RNAi in 109Q/109Q mouse striatal cells enhances cell mortality in response to serum deprivation with no effect detected in 7Q/7Q cells (***P < 0.001; ns: not significant; N = 3). The right panel shows representative western blots in which AMPKα1 siRNAs reduce AMPKα1 protein levels (N = 3, mean ± SD = 0.4 ± 0.1, P = 0.018) with no change detected in the level of Htt (N = 3, mean ± SD = 1.1 ± 0.5, P = 0.71). (C) Overexpression of an over-activated form of AMPKγ1, AMPKγ1GOF, reduces mortality of 109Q/109Q cells in response to serum deprivation (**P < 0.005, N = 3). The right panel shows representative western blots in which AMPKγ1GOF expression increases AMPKγ1 protein levels (as detected using a c-Myc tag), phosphorylated AMPKα1 levels (N = 3, mean ± SD = 1.6 ± 0.1, P = 0.027). The effect on Htt levels is addressed in (D). (D) Overexpression of the over-activated form of AMPKγ1 induces clearance of misfolded mHtt (***P < 0.001, N = 3). The right panel shows representative western blots in which AMPKγ1GOF increases AMPKγ1 levels (as detected using a c-Myc tag), and phosphorylated AMPKα levels (N = 4, mean ± SD = 1.7 ± 0.4, P = 0.021). In all panels: ns: not significant.