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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Acid sphingomyelinase inhibition improves motor behavioral deficits and neuronal loss in an amyotrophic lateral sclerosis mouse model

  • Byung Jo, Choi (KNU Alzheimer's Disease Research Institute, Kyungpook National University) ;
  • Kang Ho, Park (KNU Alzheimer's Disease Research Institute, Kyungpook National University) ;
  • Min Hee, Park (KNU Alzheimer's Disease Research Institute, Kyungpook National University) ;
  • Eric Jinsheng, Huang (Department of Pathology, University of California San Francisco) ;
  • Seung Hyun, Kim (Department of Neurology, Hanyang University College of Medicine) ;
  • Jae-sung, Bae (KNU Alzheimer's Disease Research Institute, Kyungpook National University) ;
  • Hee Kyung, Jin (KNU Alzheimer's Disease Research Institute, Kyungpook National University)
  • Received : 2022.09.13
  • Accepted : 2022.10.07
  • Published : 2022.12.31
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Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the degeneration of motor neurons in the spinal cord. Main symptoms are manifested as weakness, muscle loss, and muscle atrophy. Some studies have reported that alterations in sphingolipid metabolism may be intimately related to neurodegenerative diseases, including ALS. Acid sphingomyelinase (ASM), a sphingolipid-metabolizing enzyme, is considered an important mediator of neurodegenerative diseases. Herein, we show that ASM activity increases in samples from patients with ALS and in a mouse model. Moreover, genetic inhibition of ASM improves motor function impairment and spinal neuronal loss in an ALS mouse model. Therefore, these results suggest the role of ASM as a potentially effective target and ASM inhibition may be a possible therapeutic approach for ALS.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1A2C3006875, 2020R1A2C3006734). This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare and MSIT, Republic of Korea (HU20C0345).

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