Page 81 - Q. Neuroscience

Modulation of histone H3K4 dimethylation by polyamine improves neuropathology
and motor neuron survival in a mouse model of ALS

3,4
Ali Yousefian-Jazi , Jong-Il Kim , Neil Kowall , Hoon Ryu 1,3,4 , Junghee Lee 3,4
2
1
1 Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, South Korea;
2 Genome Medicine Institute and Department of Biochemistry, Seoul National University College of Medicine, Seoul 110-799, South Korea
3 VA Boston Healthcare System, Boston, MA 02130
4 Department of Neurology, Boston University School of Medicine, Boston, MA 02118
BACKGROUND AIM
q Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative Hypothesis: Modulation of LSD1 could lead to the
disorder characterized by progressive paralysis due to motor neuron protection of motor neurons and improves neuropathology
degeneration. of ALS.
q Epigenetic modification and transcriptional dysregulation may Aim: Investigating the basis for therapeutic approaches to
contribute to motor neuron death.
q Polyamine analogues inhibit LSD1 and are capable of reactivating target LSD1 and elucidate the mechanistic role of LSD1-
H3K4 signaling pathway in ALS pathogenesis.
genes that are pathologically silenced in the disease model.
RESULTS
1. LSD1 is induced in a cellular model of ALS 3. LSD1 knock-down by shLSD1 increases 4. LSD1 is modulated in the motor
and plays a role as a transcriptional repressor the level of H3K4me2 but not H3K4me3 neurons of an animal model of ALS

2. LSD1 is induced by oxidative stress
in motor neuronal cell line (NSC-34)

5. H3K4Me2 is reduced age-dependently 6. Spermidine protects motor neurons 7. Spermidine delays onset of disease and
in motor neurons of the spinal cord of and modulates LSD1 activity in the prolong the life span of G93A ALS mice
G93A ALS mice lumbar spinal cord in G93A ALS mice

CONCLUSION ACKNOWLEDGMENTS

This study was supported by NIH Grant (R01NS109537 to J.L.).
This study was also supported by the National Research
Foundation (NRF) Grant (NRF-2016M3C7A1904233, NRF-
2018M3C7A1056894, and NRF-2020M3E5D9079742), and the
Grant (2E30320 and 2E30762) from Korea Institute of Science and
Technology of South Korea.
Contact Information
Junghee Lee, Ph.D., Email: junghee@bu.edu
Hoon Ryu, Ph.D., E-mail: hoonryu@kist.re.kr