Astrocytes protect dopaminergic neurons against aminochrome neurotoxicity

被引:24
|
作者
Segura-Aguilar, Juan [1 ]
Mannervik, Bengt [2 ]
Inzunza, Jose [3 ]
Varshney, Mukesh [3 ]
Nalvarte, Ivan [3 ]
Munoz, Patricia [1 ,4 ]
机构
[1] Univ Chile, Mol & Clin Pharmacol ICBM, Fac Med, Santiago, Chile
[2] Stockholm Univ, Dept Biochem & Biophys, Arrhenius Labs, Stockholm, Sweden
[3] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden
[4] Univ Mayor, Fac Estudios Interdisciplinarios, Nucleo Quim & Bioquim, Santiago, Chile
基金
瑞典研究理事会;
关键词
aminochrome; astrocytes; dopamine; dopaminergic neurons; exosomes; glutathione transferase M2-2; neuroprotection; Parkinson's disease; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; UBIQUITIN-PROTEASOME; LACTATE SHUTTLE; MITOCHONDRIAL; DYSFUNCTION; EXPRESSION; PATHOLOGY; CYSTEINE; SYSTEM;
D O I
10.4103/1673-5374.335690
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1861 / 1866
页数:6
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