Acid Sphingomyelinase Inhibition Improves Motor Behavioral Deficits and Neuronal Loss in an Amyotrophic Lateral Sclerosis Mouse Model

Overview

Journal BMB Rep

Specialties Biochemistry
Molecular Biology

Date 2022 Oct 13

PMID 36229415

Authors

Byung Jo Choi

Kang Ho Park

Min Hee Park

Eric Jinsheng Huang

Seung Hyun Kim

Jae-Sung Bae

Hee Kyung Jin

Affiliations

Soon will be listed here.

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. [BMB Reports 2022; 55(12): 621-626].

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