Supplementary Materials

Supplementary Material for:

Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease

Claire E. Le Pichon, William J. Meilandt,* Sara Dominguez, Hilda Solanoy, Han Lin, Hai Ngu, Alvin Gogineni, Arundhati Sengupta Ghosh, Zhiyu Jiang, Seung-Hye Lee, Janice Maloney, Vineela D. Gandham, Christine D. Pozniak, Bei Wang, Sebum Lee, Michael Siu, Snahel Patel, Zora Modrusan, Xingrong Liu, York Rudhard, Miriam Baca, Amy Gustafson, Josh Kaminker, Richard A. D. Carano, Eric J. Huang, Oded Foreman, Robby Weimer, Kimberly Scearce-Levie, Joseph W. Lewcock*

*Corresponding author. Email: lewcock{at}dnli.com (J.W.L.); meilandt.william{at}gene.com (W.J.M.)

Published 16 August 2017, Sci. Transl. Med. 9, eaag0394 (2017)
DOI: 10.1126/scitranslmed.aag0394

This PDF file includes:

  • Materials and Methods
  • Fig. S1. p-c-Jun is expressed in ChAT-positive motor neurons of SOD1 mice, and Dlk is coexpressed with neuronal markers.
  • Fig. S2. Elevations in p-c-Jun and c-Jun are detected in mouse models of AD.
  • Fig. S3. Dlk deletion is neuroprotective by histological and behavioral measures in the SOD1 mouse model of ALS.
  • Fig. S4. SOD1 transgene copy number data for the histological and survival studies shown in Fig. 4 and fig. S3.
  • Fig. S5. PS2APP;DLKcKO behavior in the water maze and fear conditioning.
  • Fig. S6. DLK deletion in PS2APP mice results in slight elevation of plaque-associated gliosis and hAPP expression without altering BACE1.
  • Fig. S7. DLK deletion in TauP301L mice does not alter total Tau or p-Tau species.
  • Fig. S8. Chemical structure, selectivity, and pharmacokinetics of GNE-8505.
  • Fig. S9. qPCR of optic nerve crush mouse retinas for genes selected on the basis of the RNA-seq results.
  • Fig. S10. Short-term treatment with DLK inhibitors reduces p-c-Jun and total c-Jun levels in PS2APP and TauP301L mice.
  • Fig. S11. Classification of synaptic loss in the neuromuscular junction of SOD1 mice.
  • Table S1. Distribution of SOD1 mice in survival study according to euthanasia criteria.
  • Table S2. GNE-8505 inhibition constant in a DLK biochemical assay.
  • Reference (50)

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