Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1
Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1
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DOI：
10.1016/j.nbd.2009.07.010
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发表时间：
2009-11-01
影响因子：
6.1
通讯作者：
Platt, Frances M.
中科院分区：
文献类型：
--
作者：
Smith, David;Wallom, Kerri-Lee;Platt, Frances M.
C1型尼曼-匹克病（NPC 1）是一种神经退行性溶酶体疾病，其特征是鞘脂和胆固醇在晚期内吞系统中储存。与其他神经退行性疾病一样，先天免疫系统的激活发生在大脑中，导致神经炎症。因此，针对大脑中的炎症是一种潜在的临床干预策略，旨在减缓疾病进展的速度，提高生活质量。我们评估了非甾体类抗炎药（NSAID）和抗氧化剂，以确定这些药物是否在急性NPC小鼠模型中具有疾病修饰作用1。NSAID显著延长了NPC 1小鼠的寿命，并减缓了临床体征的发生。然而，抗氧化剂治疗没有显著的益处。NSAID治疗与底物减少治疗（SRT）联合导致额外的益处。这些数据表明，抗炎治疗单独或与SRT联合可能是NPC 1临床管理中有用的连续治疗。(C)2009 Elsevier Inc. All rights reserved.
Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder characterized by sphingolipid and cholesterol storage in the late endocytic system. In common with other neurodegenerative diseases, activation of the innate immune system occurs in the brain resulting in neuro-inflammation. Targeting inflammation in the brain therefore represents a potential clinical intervention strategy that aims to slow the rate of disease progression and improve quality of life.We evaluated non-steroidal anti-inflammatory drugs (NSAIDs) and an anti-oxidant to determine whether these agents are disease modifying in an acute mouse model of NPC1. NSAIDs significantly prolonged the lifespan of NPC1 mice and slowed the onset of clinical signs. However, anti-oxidant therapy was of no significant benefit. Combining NSAID therapy with substrate reduction therapy (SRT) resulted in additive benefit These data suggest that anti-inflammatory therapy may be a useful adjunctive treatment in the clinical management of NPC1, alone or combined with SRT. (C) 2009 Elsevier Inc. All rights reserved.