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Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease

  • 작성자

    Jae-sung Bae
  • 작성일자

    2024-03-22
  • 조회수

    1001
Jae-sung Bae( jsbae@knu.ac.kr )
2007-presentProfessor, Department of Physiology, School of Medicine, Kyungpook National University, South Korea,
Adjunct Professor, Kyungpook National University Hospital, South Korea
2017-2019Adjunct professor, UNIST, South Korea
2014-2021,
2023-present
Chair, Department of Physiology, School of Medicine, Kyungpook National University, South Korea
2005-2007Post-Doctoral Fellow, Department of Mental Health Sciences, Royal Free and University College Medical School, University College London, UK
2001-2005MS-PhD, Department of Veterinary Medicine, Kyungpook National University, South Korea
1994-2001BS, Department of Veterinary Medicine, Kyungpook National University, South Korea

Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease

Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood-brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.

Exp Mol Med. 2024 Feb;56(2):301-310. doi: 10.1038/s12276-024-01176-4
https://www.ncbi.nlm.nih.gov/pubmed/38337058