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Fiona Kerr, Oyinkan Sofola-Adesakin, Dobril K. Ivanov, Jemma Gatliff, Beatriz Gomez Perez-Nievas, Hélène C. Bertrand, Pedro Martinez, Rebecca Callard, Inge Snoeren, Helena M. Cochemé, Jennifer Adcott, Mobina Khericha, Jorge Iván Castillo-Quan, Geoffrey Wells, Wendy Noble, Janet Thornton, Linda Partridge
Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer’s disease
www.plosgenetics.org
www.plosgenetics.org
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4.4731 0 Td
(toxicity)Tj
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(32)Tj
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0.83 0.64 0.02 0 k
(33)Tj
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(42)Tj
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3.9571 0 Td
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(of)Tj
-35.4158 -1.2983 Td
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(34)Tj
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3.4979 0 Td
(we)Tj
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1.1055 0 Td
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(35)Tj
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4.2519 0 Td
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1.0375 0 Td
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1.7291 0 Td
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2.7439 0 Td
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(A)Tj
/F13 1 Tf
()Tj
/F9 1 Tf
(42)Tj
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(protection)Tj
4.3824 0 Td
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1.0374 0 Td
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3.7304 0 Td
(to)Tj
1.0262 0 Td
(Keap1)Tj
2.7439 0 Td
(inhibi-)Tj
-34.4237 -1.3039 Td
(tion)Tj
1.8425 0 Td
(correlates)Tj
4.0762 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.474 0 Td
(rescue)Tj
2.7496 0 Td
(of)Tj
1.0148 0 Td
(A)Tj
/F13 1 Tf
()Tj
/F9 1 Tf
(42-induced)Tj
5.9357 0 Td
(Nrf2)Tj
2.092 0 Td
(defects,)Tj
3.1918 0 Td
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3.4469 0 Td
(lithium)Tj
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2.1997 0 Td
(neuro-protection)Tj
7.1092 0 Td
(independently)Tj
5.9811 0 Td
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-19.4115 -1.2982 Td
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1.9955 0 Td
(Nrf2)Tj
2.092 0 Td
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4.3767 0 Td
(Keap1)Tj
2.7439 0 Td
(inhibition)Tj
4.2236 0 Td
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4.2122 0 Td
(the)Tj
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(sensitivity)Tj
4.2236 0 Td
(of)Tj
-35.1097 -1.2983 Td
(A)Tj
/F13 1 Tf
()Tj
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(flies)Tj
1.8085 0 Td
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4.4391 0 Td
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2.6191 0 Td
(but)Tj
1.5534 0 Td
(exerted)Tj
3.1521 0 Td
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3.6227 0 Td
(protection)Tj
4.3823 0 Td
(against)Tj
3.0274 0 Td
(oxidative)Tj
-32.5188 -1.3039 Td
(damage)Tj
3.3221 0 Td
(in)Tj
1.0375 0 Td
(comparison)Tj
4.9776 0 Td
(to)Tj
1.0205 0 Td
(lithium)Tj
3.1748 0 Td
(treatment.)Tj
4.3596 0 Td
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(modulation)Tj
4.9039 0 Td
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(and)Tj
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(lithium)Tj
-32.7682 -1.2983 Td
(additively)Tj
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(against)Tj
3.0273 0 Td
(A)Tj
/F13 1 Tf
()Tj
/F9 1 Tf
(42)Tj
2.3414 0 Td
(toxicity,)Tj
3.4299 0 Td
(in)Tj
1.0319 0 Td
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1.9955 0 Td
(either)Tj
2.5342 0 Td
(treatment)Tj
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(alone,)Tj
2.6078 0 Td
(but)Tj
1.5534 0 Td
(did)Tj
-35.7616 -1.2983 Td
(not)Tj
1.5703 0 Td
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2.109 0 Td
(respective)Tj
4.1839 0 Td
(effects)Tj
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(on)Tj
1.2756 0 Td
(xenobiotic)Tj
4.4333 0 Td
(and)Tj
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3.5489 0 Td
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(the)Tj
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(of)Tj
1.0148 0 Td
(these)Tj
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(manipulations.)Tj
6.2192 0 Td
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6.3723 0 Td
(n)Tj
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(of)Tj
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(Keap1)Tj
2.7439 0 Td
(alone)Tj
2.3811 0 Td
(addi-)Tj
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(tionally)Tj
3.2144 0 Td
(protected)Tj
4.0082 0 Td
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(A)Tj
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()Tj
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(42)Tj
2.3357 0 Td
(toxicity)Tj
3.1975 0 Td
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(mechanisms)Tj
5.1987 0 Td
(correlating)Tj
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(enhanced)Tj
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(degradation)Tj
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(of)Tj
1.0147 0 Td
(A)Tj
/F13 1 Tf
()Tj
/F9 1 Tf
(42)Tj
2.3414 0 Td
(peptide.)Tj
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3.1464 0 Td
(our)Tj
1.6271 0 Td
(data)Tj
1.9105 0 Td
(highlight)Tj
3.8154 0 Td
(Keap1)Tj
2.7439 0 Td
(as)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(efficient)Tj
3.4469 0 Td
(target)Tj
2.5115 0 Td
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(the)Tj
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(amelioration)Tj
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(of)Tj
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(Nrf2)Tj
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3.8267 0 Td
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(AD.)Tj
1.8652 0 Td
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3.1691 0 Td
(we)Tj
1.3266 0 Td
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1.389 0 Td
(the)Tj
1.4683 0 Td
(first)Tj
1.8028 0 Td
(time)Tj
2.0296 0 Td
(that)Tj
1.7802 0 Td
(a)Tj
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6.7577 0 Td
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2.5342 0 Td
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4.9663 0 Td
(protein-protein)Tj
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(22)Tj
0 g
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(indeed)Tj
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()Tj
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(data)Tj
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(suggest)Tj
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1.4683 0 Td
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1.3889 0 Td
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1.8652 0 Td
(and)Tj
1.7291 0 Td
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4.4617 0 Td
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(neuro-)Tj
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5.278 0 Td
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BT
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Q
q
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(13)Tj
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4.6884 0 Td
(at)Tj
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4.2293 0 Td
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3.1408 0 Td
(A)Tj
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()Tj
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(A)Tj
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(42)Tj
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(peptides)Tj
3.5603 0 Td
(may)Tj
1.9275 0 Td
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4.5694 0 Td
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(this)Tj
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(effect.)Tj
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(Nrf2/cncC)Tj
4.4787 0 Td
(reporter)Tj
3.5036 0 Td
(flies)Tj
1.8028 0 Td
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/F14 1 Tf
[(\n)-3()9()]TJ
/F9 1 Tf
(-GFP;)Tj
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([)Tj
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(35)Tj
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3.0047 0 Td
(induction)Tj
4.1386 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
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(site-directed,)Tj
5.4085 0 Td
(copy)Tj
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(of)Tj
-36.4419 -1.3039 Td
(Arctic)Tj
2.6872 0 Td
(mutant)Tj
3.1464 0 Td
(A)Tj
/F13 1 Tf
()Tj
/F9 1 Tf
(42)Tj
2.3414 0 Td
(\(ArcA)Tj
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