Alzheimer's disease: An acquired neurodegenerative laminopathy.
Alzheimer's disease: An acquired neurodegenerative laminopathy.
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DOI：
10.1080/19491034.2016.1183859
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发表时间：
2016-05-03
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影响因子：
--
通讯作者：
Frost B
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作者：
Frost B
细胞核通常被描绘为被核膜光滑表面包围的球体。对于大多数细胞类型，这种描述是准确的。然而，在其他细胞类型和某些病理条件下，光滑的核外部被核膜（通常称为“核质网”）的管状内陷打断，进入核内部深处。我们最近报道了死后人类阿尔茨海默病脑组织中核质网的显着扩张。我们发现核骨架（一种覆盖内核膜和相关内陷的富含核纤层蛋白的网状结构）的功能障碍是体内与阿尔茨海默病相关的神经变性的原因。此外，我们证明了核骨架的适当功能是成体神经元存活和维持基因组结构所必需的。在这里，我们详细阐述了这些发现在病理状态和生理衰老方面的意义，并讨论了核膜内陷的细胞原因和后果。
The nucleus is typically depicted as a sphere encircled by a smooth surface of nuclear envelope. For most cell types, this depiction is accurate. In other cell types and in some pathological conditions, however, the smooth nuclear exterior is interrupted by tubular invaginations of the nuclear envelope, often referred to as a “nucleoplasmic reticulum,” into the deep nuclear interior. We have recently reported a significant expansion of the nucleoplasmic reticulum in postmortem human Alzheimer's disease brain tissue. We found that dysfunction of the nucleoskeleton, a lamin-rich meshwork that coats the inner nuclear membrane and associated invaginations, is causal for Alzheimer's disease-related neurodegeneration in vivo. Additionally, we demonstrated that proper function of the nucleoskeleton is required for survival of adult neurons and maintaining genomic architecture. Here, we elaborate on the significance of these findings in regard to pathological states and physiological aging, and discuss cellular causes and consequences of nuclear envelope invagination.