Mennini Tiziana, De Paola Massimiliano, Bigini Paolo, Mastrotto Cristina, Fumagalli Elena, Barbera Sara, Mengozzi Manuela, Viviani Barbara, Corsini Emanuela, Marinovich Marina, Torup Lars, Van Beek Johan, Leist Marcel, Brines Michael, Cerami Antony, Ghezzi Pietro
Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy.
Mol Med. 2006 Jul-Aug;12(7-8):153-60. doi: 10.2119/2006-00045.Mennini.
Chronic treatment with asialo erythropoietin (ASIALO-EPO) or carbamylated erythropoietin (CEPO) improved motor behavior and reduced motoneuron loss and astrocyte and microglia activation in the cervical spinal cord of wobbler mice, an animal model of amyotrophic lateral sclerosis, but had no effect on hematocrit values. ASIALO-EPO and CEPO, like the parent compound EPO, protected primary motoneuron cultures from kainate-induced death in vitro. Both EPO receptor and the common CD131 beta chain were expressed in cultured motoneurons and in the anterior horn of wobbler mice spinal cord. Our results strongly support a role for the common beta chain CD131 in the protective effect of EPO derivatives on motoneuron degeneration. Thus CEPO, which does not bind to the classical homodimeric EPO receptor and is devoid of hematopoietic activity, could be effective in chronic treatment aimed at reducing motoneuron degeneration.
用去唾液酸促红细胞生成素（ASIALO-EPO）或氨甲酰化促红细胞生成素（CEPO）进行长期治疗，可改善运动行为，并减少运动神经元损失以及星形胶质细胞和小胶质细胞的激活，这些变化发生在肌萎缩侧索硬化症动物模型——摇摆小鼠的颈脊髓中，但对血细胞比容值没有影响。与母体化合物促红细胞生成素（EPO）一样，ASIALO-EPO和CEPO在体外可保护原代运动神经元培养物免受海藻酸盐诱导的死亡。促红细胞生成素受体和共同的CD131β链在培养的运动神经元以及摇摆小鼠脊髓前角中均有表达。我们的结果有力地支持了共同的β链CD131在促红细胞生成素衍生物对运动神经元变性的保护作用中所起的作用。因此，不与经典的同二聚体促红细胞生成素受体结合且缺乏造血活性的CEPO，可能对旨在减少运动神经元变性的长期治疗有效。
