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• W2736738208 abstract "Abstract LINE-1 mobile genetic elements have shaped the mammalian genome during evolution. A minority of them have escaped fossilization which, when activated, can threaten genome integrity. We report that LINE-1 are expressed in substantia nigra ventral midbrain dopaminergic neurons, a class of neurons that degenerate in Parkinson disease. In Engrailed-1 heterozygotes, these neurons show a progressive degeneration that starts at 6 weeks of age, coinciding with an increase in LINE-1 expression. Similarly, DNA damage and cell death, induced by an acute oxidative stress applied to embryonic midbrain neurons in culture or to adult midbrain dopaminergic neurons in vivo , are accompanied by enhanced LINE-1 expression. Reduction of LINE-1 activity through (i) direct transcriptional repression by Engrailed, (ii) a siRNA directed against LINE-1, (iii) the nucleoside-analogue reverse transcriptase inhibitor stavudine and (iv) viral Piwil1 expression, protects against oxidative stress in vitro and in vivo . We thus propose that LINE-1 overexpression triggers oxidative stress-induced DNA strand breaks and that an Engrailed adult function is to protect mesencephalic dopaminergic neurons through the repression of LINE-1 expression." @default.
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• W2736738208 date "2017-07-19" @default.
• W2736738208 modified "2023-10-17" @default.
• W2736738208 title "Engrailed homeoprotein blocks degeneration in adult dopaminergic neurons through LINE-1 repression" @default.
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• W2736738208 doi "https://doi.org/10.1101/164608" @default.
• W2736738208 hasPublicationYear "2017" @default.
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