배재성 (경북대학교 의과대학)

한빛사논문

조회239

경북대학교 의과대학

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Exp. Mol. Med., Feb 09 2024, | https://doi.org/10.1038/s12276-024-01176-4 Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease

Byung Jo Choi^1,2,4, Min Hee Park^1,2,4, Hee Kyung Jin^1,3,4 and Jae-sung Bae^1,2

¹KNU Alzheimer’s Disease Research Institute, Kyungpook National University, Daegu 41566, South Korea.

²Department of Physiology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea.

³Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, South Korea.

⁴These authors contributed equally: Byung Jo Choi, Min Hee Park, Hee Kyung Jin.

Corresponding author : Correspondence to Jae-sung Bae.

Abstract

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.

논문정보

형식Review Paper
게재일2024년 02월 (BRIC 등록일 2024-02-20)
연구진국내 연구진
분야 의약학 > 신경의학

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