Lukiw W J, Krishnan B, Wong L, Kruck T P, Bergeron C, Crapper McLachlan D R
Center for Research in Neurodegenerative Disease, University of Toronto, Canada.
Neurobiol Aging. 1992 Jan-Feb;13(1):115-21. doi: 10.1016/0197-4580(92)90018-s.
Senile dementia of the Alzheimer type (AD) is a fatal encephalopathy of uncertain etiology. Whether the neurotoxin aluminum plays any role in the AD process in unknown. Here we report an increased amount of aluminum in a chromatin subcompartment, the micrococcal nuclease (MN; EC 3.1.31.1) accessible dinucleosome fraction, in neocortical nuclei isolated from 17 control and 21 AD-affected brains. At these MN-accessible loci we also observe an increase in H1 zero linker histone proteins, DNA-binding proteins which are thought to act as regulators of chromatin compaction. These data support the hypothesis that one deleterious effect of aluminum upon nuclear structure in AD-afflicted brain may be to condense brain chromatin nonrandomly through an interaction with H1 zero linker protein and thereby alter the ability of brain DNA to be effectively transcribed.
阿尔茨海默病型老年痴呆症（AD）是一种病因不明的致命性脑病。神经毒素铝是否在AD发病过程中起作用尚不清楚。在此，我们报告从17例对照大脑和21例AD患者大脑中分离出的新皮质细胞核中，染色质亚区室（微球菌核酸酶（MN；EC 3.1.31.1）可及的双核小体部分）中的铝含量增加。在这些MN可及位点，我们还观察到H1零连接组蛋白的增加，H1零连接组蛋白是一种DNA结合蛋白，被认为是染色质压缩的调节因子。这些数据支持这样的假说：铝对AD患者大脑核结构的一种有害作用可能是通过与H1零连接蛋白相互作用，使大脑染色质非随机浓缩，从而改变大脑DNA有效转录的能力。
