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Author Notes:

Correspondence and requests for materials should be addressed to D.J.K. (email: djkatz@emory.edu)

M.A.C. and D.A.M. contributed equally to this work.

D.J.K. worked on the design and execution of the experiments as well as the writing of the manuscript.

A.K.E., K.A.P.-S., and D.W. assisted with experiments.

B.G.B. and J.M.B. contributed to all of the bioinformatic analyses.

A.I.L. assisted with obtaining and analyzing the human pathology and provided guidance throughout.

The manuscript was edited by all the coauthors.

We thank M. Rosenfeld (U.C.S.D) for providing the LSD1 mice; N. Seyfried, R. Betarbet, M. Gearing, J. Fritz, and D. Cooper from the Emory ADRC (P50 AG025688), NINDS Emory Neuroscience Core Facilities (P30NS055077), A. Katz and S. Katz, for assistance with analyses of human tissue; J. Schroeder from the Emory Rodent Behavioral Core for help with behavioral assays; G. Pavlath for assistance with muscle histology; E. Corgiat for the myelination data; G. Bassell, V. Faundez, J. Boss, B. Kelly, C. Bean and T. Caspary for comments on the manuscript and assistance throughout; R. Tenser for introducing us to A. Levey; and all of the Katz Lab for contributions throughout.

D.J.K. would like to thank J. Cohen, F. Turano, H. Lyman and S. Tilghman; D.A.M. would like to thank L. Myrick and A. Myrick; and M.A.C. would like to thank R. Cordeiro and Y. France for help along the way.

A.K.E. would like to thank A. Wiemer and P. Engstrom.

The authors declare no competing financial interests.


Research Funding:

D.A.M. was supported by the Emory PREP Post-Bac Program (5R25GM089615-04); and M.A.C. and B.G.B. by the GMB training grant (T32GM008490-21).

B.G.B. was supported by NIH pre-doctoral fellowship F31AI11226101.

A.K.E. was supported by the BCDB training grant (T32GM008367-26).

D.W. was supported by AG0476678 and KPS was supported by NS098615.

The work was supported by a grant to D.J.K. from the National Institute of Neurological Disorders and Stroke (1R01NS087142).


  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • Epigenetics
  • Epigenetics and behaviour

LSD1 protects against hippocampal and cortical neurodegeneration

Journal Title:

Nature Communications


Volume 8


, Pages 805-805

Type of Work:

Article | Final Publisher PDF


To investigate the mechanisms that maintain differentiated cells, here we inducibly delete the histone demethylase LSD1/KDM1A in adult mice. Loss of LSD1 leads to paralysis, along with widespread hippocampus and cortex neurodegeneration, and learning and memory defects. We focus on the hippocampus neuronal cell death, as well as the potential link between LSD1 and human neurodegenerative disease and find that loss of LSD1 induces transcription changes in common neurodegeneration pathways, along with the re-activation of stem cell genes, in the degenerating hippocampus. These data implicate LSD1 in the prevention of neurodegeneration via the inhibition of inappropriate transcription. Surprisingly, we also find that transcriptional changes in the hippocampus are similar to Alzheimer's disease (AD) and frontotemporal dementia (FTD) cases, and LSD1 is specifically mislocalized to pathological protein aggregates in these cases. These data raise the possibility that pathological aggregation could compromise the function of LSD1 in AD and FTD.

Copyright information:

© 2017 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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