생화학분자생물학회

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