Open AccessN6-Furfuryladenine is protective in Huntington’s disease models by signaling huntingtin phosphorylation
Author(s) -
Laura E. Bowie,
Tamara Maiuri,
Melanie Alpaugh,
Michelle Gabriel,
Nicolas Arbez,
Danny Galleguillos,
Claudia Lin-Kar Hung,
Shreya Patel,
Jianrun Xia,
Nicholas T. Hertz,
Christopher A. Ross,
David W. Litchfield,
Simonetta Sipione,
Ray Truant
Publication year - 2018
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1801772115
Subject(s) - huntingtin , huntington's disease , phosphorylation , dna damage , mutant , microbiology and biotechnology , dna , mechanism (biology) , dna repair , signal transduction , biology , huntingtin protein , mutation , chemistry , genetics , disease , gene , medicine , physics , quantum mechanics
Significance We have discovered a molecule derived from DNA-damage repair that can correct the lack of phosphorylation of mutant huntingtin, the cause of Huntington’s disease (HD). In a mouse model, treatment reverses HD-like disease, and we see the lowering of mutant huntingtin levels to normal. The mechanism of this molecule is that it is processed to make a signal for kinase activity essential for repairing DNA. This mechanism is critical when neurons are stressed and have very low or absent energy levels. We propose that this molecule is a type of signaling from DNA-damage repair that occurs at dangerously low ATP levels.
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