Broccardo Cyril, Nieoullon Vincent, Amin Rada, Masmejean Frédérique, Carta Sonia, Tassi Sara, Pophillat Matthieu, Rubartelli Anna, Pierres Michel, Rougon Geneviève, Nieoullon André, Chazal Genèvieve, Chimini Giovanna
Centre d'Immunologie de Marseille Luminy INSERM CNRS, Université de la Méditerranée Marseille, France.
J Neurochem. 2006 Apr;97(2):345-55. doi: 10.1111/j.1471-4159.2006.03714.x. Epub 2006 Mar 15.
The notion that the ATP-binding cassette transporter-A2 (ABCA2) may be involved in brain sterol homeostasis and is associated with early onset Alzheimer's disease led us to explore its neural expression. Our data support and extend the previous reports on ABCA2 expression by oligodendrocytes. They evidence that ABCA2 (i) is located in intracellular vesicles, identified in transfected cells as lysosome-related organelles only partially overlapping with classical endolysosomes; (ii) is a marker of neural progenitors as it is expressed in the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampal formation, sites of continual neurogenesis in the adult brain, and in nestin(+) cells differentiated in vitro from embryonic stem cells; (iii) persists, in the adult rodent brain, in a subset of GABAergic and glutamatergic neurons. Considering that the latter are targets of Alzheimer's lesions, these data provide a new rationale to explore the neuropathological consequences of ABCA2 functional dysregulations.
ATP结合盒转运蛋白A2（ABCA2）可能参与脑内固醇稳态并与早发性阿尔茨海默病相关的这一观点，促使我们去探究其在神经中的表达。我们的数据支持并拓展了先前关于少突胶质细胞表达ABCA2的报道。这些数据表明ABCA2：（i）位于细胞内囊泡中，在转染细胞中被鉴定为仅与经典内溶酶体部分重叠的溶酶体相关细胞器；（ii）是神经祖细胞的标志物，因为它在侧脑室的室下区和海马结构的齿状回中表达，这两个部位是成人大脑中持续神经发生的场所，并且在体外从胚胎干细胞分化而来的巢蛋白阳性细胞中也有表达；（iii）在成年啮齿动物脑中，在一部分γ-氨基丁酸能和谷氨酸能神经元中持续存在。鉴于后者是阿尔茨海默病病变的靶点，这些数据为探究ABCA2功能失调的神经病理学后果提供了新的理论依据。
