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Acid sphingomyelinase inhibition improves motor behavioral deficits and neuronal loss in an amyotrophic lateral sclerosis mouse model

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초록

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerativedisease characterized by the degeneration of motorneurons in the spinal cord. Main symptoms are manifested asweakness, muscle loss, and muscle atrophy. Some studies havereported that alterations in sphingolipid metabolism may beintimately related to neurodegenerative diseases, including ALS. Acid sphingomyelinase (ASM), a sphingolipid-metabolizing enzyme,is considered an important mediator of neurodegenerativediseases. Herein, we show that ASM activity increases insamples from patients with ALS and in a mouse model. Moreover,genetic inhibition of ASM improves motor function impairmentand spinal neuronal loss in an ALS mouse model. Therefore, these results suggest the role of ASM as a potentiallyeffective target and ASM inhibition may be a possible therapeuticapproach for ALS.

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerativedisease characterized by the degeneration of motorneurons in the spinal cord. Main symptoms are manifested asweakness, muscle loss, and muscle atrophy. Some studies havereported that alterations in sphingolipid metabolism may beintimately related to neurodegenerative diseases, including ALS. Acid sphingomyelinase (ASM), a sphingolipid-metabolizing enzyme,is considered an important mediator of neurodegenerativediseases. Herein, we show that ASM activity increases insamples from patients with ALS and in a mouse model. Moreover,genetic inhibition of ASM improves motor function impairmentand spinal neuronal loss in an ALS mouse model. Therefore, these results suggest the role of ASM as a potentiallyeffective target and ASM inhibition may be a possible therapeuticapproach for ALS.

참고문헌 (33)

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