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

Authors :
Byung Jo Choi
Min Hee Park
Hee Kyung Jin
Jae-sung Bae
Source :
Experimental and Molecular Medicine, Vol 56, Iss 2, Pp 301-310 (2024)
Publication Year :
2024
Publisher :
Nature Publishing Group, 2024.

Abstract

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.

Subjects

Subjects :
Medicine
Biochemistry
QD415-436

Details

Language :
English
ISSN :
20926413
Volume :
56
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Experimental and Molecular Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.b4a2933386c45fe81edf0e0a655241c
Document Type :
article
Full Text :
https://doi.org/10.1038/s12276-024-01176-4