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Nat Commun. 2017 Oct 9;8(1):805. doi: 10.1038/s41467-017-00922-9.

LSD1 protects against hippocampal and cortical neurodegeneration.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
2
Graduate Division of Biological and Biomedical Science, Emory University, Atlanta, GA, 30322, USA.
3
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
4
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
5
Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
6
Emory University Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, 30322, USA.
7
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA. djkatz@emory.edu.

Abstract

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."LSD1 is a histone demethylase that plays many roles during development. Here, the authors provide evidence that loss of LSD1 in adult mice leads to paralysis and neurodegeneration in the hippocampus and cortex and suggest a potential link between LSD1 and human neurodegenerative disease.

PMID:
28993646
PMCID:
PMC5634471
DOI:
10.1038/s41467-017-00922-9
[Indexed for MEDLINE]
Free PMC Article

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