Daoud H, Valdmanis PN, Gros-Louis F, Belzil V, Spiegelman D, Henrion E, Diallo O, Desjarlais A, Gauthier J, Camu W, Dion PA, Rouleau GA.
Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis.
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Thank you for this well-written article.
I would like to add this recent study, which showed that nucleic acid binding activity is required for TDP-43-mediated toxicity in flies.
C-terminal fragments of TDP-43 lack such activity, but are still capable of forming aggregates. This supports the hypothesis that the aggregates themselves are not toxic, and that instead, the toxicity is related to a modulation of the endogenous function of this nucleic acid binding protein.
Therefore, studies addressing its DNA and RNA targets may be very important in understanding TDP-43-mediated neurodegeneration.
Voigt A, Herholz D, Fiesel FC, Kaur K, Müller D, Karsten P, Weber SS, Kahle PJ, Marquardt T, Schulz JB.
TDP-43-mediated neuron loss in vivo requires RNA-binding activity.
PLoS One. 2010;5(8):e12247.
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