Auderset Loic, Pitman Kimberley A, Cullen Carlie L, Pepper Renee E, Taylor Bruce V, Foa Lisa, Young Kaylene M
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
School of Medicine, University of Tasmania, Hobart, TAS, Australia.
Front Cell Dev Biol. 2020 Nov 13;8:564351. doi: 10.3389/fcell.2020.564351. eCollection 2020.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a large, endocytic cell surface receptor that is highly expressed by oligodendrocyte progenitor cells (OPCs) and LRP1 expression is rapidly downregulated as OPCs differentiate into oligodendrocytes (OLs). We report that the conditional deletion of from adult mouse OPCs ( ) increases the number of newborn, mature myelinating OLs added to the corpus callosum and motor cortex. As these additional OLs extend a normal number of internodes that are of a normal length, -deletion increases adult myelination. OPC proliferation is also elevated following deletion , however, this may be a secondary, homeostatic response to increased OPC differentiation, as our experiments show that LRP1 is a direct negative regulator of OPC differentiation, not proliferation. Deleting from adult OPCs also increases the number of newborn mature OLs added to the corpus callosum in response to cuprizone-induced demyelination. These data suggest that the selective blockade of LRP1 function on adult OPCs may enhance myelin repair in demyelinating diseases such as multiple sclerosis.
低密度脂蛋白受体相关蛋白1（LRP1）是一种大型的内吞性细胞表面受体，在少突胶质前体细胞（OPC）中高度表达，并且随着OPC分化为少突胶质细胞（OL），LRP1的表达会迅速下调。我们报告称，成年小鼠OPC中LRP1的条件性缺失（ ）会增加胼胝体和运动皮层中新增的成熟髓鞘形成OL的数量。由于这些额外的OL延伸出正常数量且长度正常的节间，LRP1缺失会增加成年期的髓鞘形成。LRP1缺失后OPC增殖也会升高，然而，这可能是对OPC分化增加的一种继发性稳态反应，因为我们的 实验表明LRP1是OPC分化而非增殖的直接负调节因子。从成年OPC中删除LRP1也会增加在铜离子螯合剂诱导的脱髓鞘反应中胼胝体中新增的成熟OL的数量。这些数据表明，对成年OPC上LRP1功能的选择性阻断可能会增强脱髓鞘疾病如多发性硬化症中的髓鞘修复。
