中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 1861-1866.doi: 10.4103/1673-5374.335690

• 综述:神经损伤修复保护与再生 •    下一篇

星形胶质细胞保护多巴胺能神经元免受氨基色素神经毒害

  

  • 出版日期:2022-09-15 发布日期:2022-03-03

Astrocytes protect dopaminergic neurons against aminochrome neurotoxicity

Juan Segura-Aguilar1, *, Bengt Mannervik2, José Inzunza3, Mukesh Varshney3, Ivan Nalvarte3, Patricia Muñoz1, 4   

  1. 1Molecular and Clinical Pharmacology ICBM Faculty of Medicine University of Chile, Santiago, Chile; 2Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden; 3Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; 4Nucleo de Química y Bioquímica, Facultad de Estudios Interdisciplinarios, Universidad Mayor, Santiago, Chile
  • Online:2022-09-15 Published:2022-03-03
  • Contact: Juan Segura-Aguilar, PhD, jsegura@med.uchile.cl.
  • Supported by:
    This work was supported by ANID-FONDECYT 1170033 (to JSA), ANID-STINT-CONICYT CS2018-7940 (to JSA, IN, JI, MV), Swedish Research Council grant 2015-04222 to BM.

摘要: Neural Regen Res:新的星形胶质细胞保护机制在帕金森病中的作用 
星形胶质细胞通过调节神经元功能和存活来保护神经元。星形胶质细胞以多种方式支持神经元。它们通过星形胶质细胞 - 神经元乳酸穿梭提供能量,保护神经元免受兴奋性毒性,并内化神经元脂滴以降解脂肪酸从而提供神经元代谢和突触支持。最近报道了一种星形胶质细胞系统,用于保护多巴胺神经元免受多巴胺的神经毒性产物,如氨基色素和其他邻醌,这些产物是在神经黑色素合成下通过氧化多巴胺儿茶酚结构产生的。星形胶质细胞通过外泌体分泌谷胱甘肽转移酶 M2-2,将这种酶转运到多巴胺能神经元中,以保护这些神经元免受氨基色素神经毒性的影响。 
来自智利大学医学院的Juan Segura-Aguilar团队认为,新的星形胶质细胞神经保护机制中,星形胶质细胞分泌的GSTM2可防止多巴胺能神经元中的邻醌依赖性神经毒性。这些神经元不表达 GSTM2,但星形胶质细胞表达这种酶。然而,星形胶质细胞分泌的 GSTM2 可以被多巴胺能神经元内化,从而保护多巴胺能神经元免受邻醌的有害影响。星形胶质细胞分泌 GSTM2 是由外泌体释放介导的,这解释了多巴胺神经元将 GSTM2 内化到细胞质中以介导对邻醌的保护的能力。这种新的星形胶质细胞保护机制在多巴胺氧化为神经黑色素期间对多巴胺神经元中邻醌神经毒性的保护机制对于防止超过 DT-心肌黄酶保护能力时黑质中多巴胺能神经元的损失非常重要。 
文章在《中国神经再生研究(英文版)》杂志2022年9 月 9 期发表。
https://orcid.org/0000-0002-1018-673X (Juan Segura-Aguilar); https://orcid.org/0000-0002-6416-064X (Bengt Mannervik); 
https://orcid.org/0000-0003-0876-6767 (José Inzunza); https://orcid.org/0000-0003-2165-0152 (Mukesh Varshney); 
https://orcid.org/0000-0001-6828-2583 (Ivan Nalvarte); https://orcid.org/0000-0001-6596-9451 (Patricia Muñoz)

Abstract: Astrocytes protect neurons by modulating neuronal function and survival. Astrocytes support neurons in several ways. They provide energy through the astrocyte-neuron lactate shuttle, protect neurons from excitotoxicity, and internalize neuronal lipid droplets to degrade fatty acids for neuronal metabolic and synaptic support, as well as by their high capacity for glutamate uptake and the conversion of glutamate to glutamine. A recent reported astrocyte system for protection of dopamine neurons against the neurotoxic products of dopamine, such as aminochrome and other o-quinones, were generated under neuromelanin synthesis by oxidizing dopamine catechol structure. Astrocytes secrete glutathione transferase M2-2 through exosomes that transport this enzyme into dopaminergic neurons to protect these neurons against aminochrome neurotoxicity. The role of this new astrocyte protective mechanism in Parkinson´s disease is discussed.

Key words: aminochrome, astrocytes, dopamine, dopaminergic neurons, exosomes, glutathione transferase M2-2, neuroprotection, Parkinson’s disease