Genetic dissection of a cell-autonomous neurodegenerative disorder: lessons learned from mouse models of Niemann-Pick disease type C.
Genetic dissection of a cell-autonomous neurodegenerative disorder: lessons learned from mouse models of Niemann-Pick disease type C.
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DOI：
10.1242/dmm.012385
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发表时间：
2013-09
影响因子：
4.3
通讯作者：
Scott MP
中科院分区：
文献类型：
--
作者：
Lopez ME;Scott MP
了解神经退行性疾病的进展及其治疗需要对相关细胞类型和分子途径进行系统的表征和操作。神经退行性溶酶体储存障碍C型尼曼-皮克病(NPC)是一种高度易感的遗传学方法，可以在生物、细胞和分子水平上探索疾病生物学。尽管鼻咽癌是一种罕见的疾病，但对相关神经病理的遗传分析有望提供对疾病神经回路、选择性神经元脆弱性和神经-神经胶质相互作用的逻辑的洞察。能够自主地在自然发生的动物模型中控制这种紊乱的细胞，概括了人类疾病的许多方面，这使得在体内对这种疾病的神经生物学进行了无与伦比的剖析。在这里，我们回顾了基于小鼠模型的鼻咽癌疾病研究的进展，特别是NPC1的缺陷引起的亚型，NPC1是一种参与脂质运输的类固醇结合的晚期内膜蛋白。我们还讨论了鼻咽癌疾病研究的最新发现和未来方向，这些研究与理解神经变性的细胞和分子机制有关。
Understanding neurodegenerative disease progression and its treatment requires the systematic characterization and manipulation of relevant cell types and molecular pathways. The neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NPC) is highly amenable to genetic approaches that allow exploration of the disease biology at the organismal, cellular and molecular level. Although NPC is a rare disease, genetic analysis of the associated neuropathology promises to provide insight into the logic of disease neural circuitry, selective neuron vulnerability and neural-glial interactions. The ability to control the disorder cell-autonomously and in naturally occurring spontaneous animal models that recapitulate many aspects of the human disease allows for an unparalleled dissection of the disease neurobiology in vivo. Here, we review progress in mouse-model-based studies of NPC disease, specifically focusing on the subtype that is caused by a deficiency in NPC1, a sterol-binding late endosomal membrane protein involved in lipid trafficking. We also discuss recent findings and future directions in NPC disease research that are pertinent to understanding the cellular and molecular mechanisms underlying neurodegeneration in general.
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影响因子：
4.3
作者：
Farfel-Becker T;Vitner EB;Futerman AH
通讯作者：
Futerman AH
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
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作者：
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通讯作者：
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3.5
作者：
Blom, TS;Linder, MD;Ikonen, E
通讯作者：
Ikonen, E
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作者：
Igaz, Lionel M.;Kwong, Linda K.;Lee, Virginia M. -Y.
通讯作者：
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