A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP-Associated Multisystem Proteinopathy.
A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP-Associated Multisystem Proteinopathy.
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DOI：
10.1371/journal.pone.0131995
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nalbandian A
中科院分区：
文献类型：
--
作者：
Llewellyn KJ;Walker N;Nguyen C;Tan B;BenMohamed L;Kimonis VE;Nalbandian A
有效的治疗方法和潜在的疾病机制的发现valosin含有蛋白质（VCP）相关的肌病和神经退行性疾病仍然难以捉摸。由VCP基因突变引起的VCP疾病是一组临床和遗传异质性疾病，其表现不同于遗传性包涵体肌病、佩吉特骨病、额颞叶痴呆（IBMPFD）和肌萎缩侧索硬化（ALS）。在本研究中，我们通过免疫组织化学和生化测定，研究了较高的饮食脂质百分比对VCPR 155 H/R155 H、VCPR 155 H/+和野生型（WT）小鼠从出生到15月龄的影响。研究结果表明，当喂食9%富含脂质的饮食（LED）时，杂合子小鼠的肌肉力量，组织学和自噬信号通路得到改善。然而，将LED增加12%、30%和48%并未改善纯合子和杂合子的存活率、肌肉病理学、脂质积累或自噬级联。这些发现表明，平衡的脂质补充可能是VCP相关多系统蛋白质病患者的治疗策略。
The discovery of effective therapies and of disease mechanisms underlying valosin containing protein (VCP)-associated myopathies and neurodegenerative disorders remains elusive. VCP disease, caused by mutations in the VCP gene, are a clinically and genetically heterogeneous group of disorders with manifestations varying from hereditary inclusion body myopathy, Paget’s disease of bone, frontotemporal dementia (IBMPFD), and amyotrophic lateral sclerosis (ALS). In the present study, we examined the effects of higher dietary lipid percentages on VCPR155H/R155H, VCPR155H/+ and Wild Type (WT) mice from birth until 15 months of age by immunohistochemical and biochemical assays. Findings illustrated improvement in the muscle strength, histology, and autophagy signaling pathway in the heterozygote mice when fed 9% lipid-enriched diets (LED). However, increasing the LED by 12%, 30%, and 48% showed no improvement in homozygote and heterozygote survival, muscle pathology, lipid accumulation or the autophagy cascade. These findings suggest that a balanced lipid supplementation may have a therapeutic strategy for patients with VCP-associated multisystem proteinopathies.
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影响因子：
3.8
作者：
Luan, Guoming;Zhao, Yanxin;Li, Tianfu
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DOI：
10.1111/j.1752-8062.2012.00407.x
发表时间：
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期刊：
Clinical and translational science
影响因子：
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作者：
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影响因子：
4.8
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通讯作者：
Verheijen, Mark H. G.