pLG72 is a primate-specific protein of enigmatic function that was proposed to modulate mitochondria fragmentation and the activity of the peroxisomal enzyme D-amino acid oxidase (DAAO). DAAO is deputed to degradation of the NMDA receptor co-agonist D-serine in human brain and the R199W substitution in DAAO was identified in a familial case of amyotrophic lateral sclerosis (ALS). A recent work reported that U87 glioblastoma cells ectopically expressing pLG72 showed a lower proliferation, produced superoxide radicals, induced SOD1 aggregation and decreased its activity. Because of the role of SOD1 in eliminating ROS species and its relevance in ALS we evaluated the link between pLG72 and SOD1 using both wild-type pLG72 and its R30K variant related to schizophrenia susceptibility. In vitro studies on recombinant proteins excluded the establishment of a stable complex and that pLG72 could affect SOD1 activity and stability. At cellular level, ectopic expression of pLG72 in glioblastoma U87 cells did not affect cell viability and ROS/superoxide production: only caspase activity (a marker of apoptosis) was slightly increased in cells expressing the R30K pLG72 variant. SOD1 and pLG72 did not colocalize in transfected U87 glioblastoma cells: pLG72 largely localized to mitochondria marker and SOD1 was largely cytosolic. Moreover, the ectopic expression of pLG72 appeared not to alter the expression of SOD1 and its aggregation. Altogether, the combination of biochemical and cellular studies allow to exclude that pLG72 modulates SOD1 function and aggregation, thus that it could play a role in ALS susceptibility.

pLG72是具有神秘功能的灵长类动物特异性蛋白，被提议用于调节线粒体片段化和过氧化物酶体酶D-氨基酸氧化酶（DAAO）的活性。DAAO被认为可导致人脑中NMDA受体激动剂D-丝氨酸的降解，并在家族性肌萎缩性侧索硬化症（ALS）病例中发现DAAO中的R199W取代。最近的一项工作报道，异位表达pLG72的U87胶质母细胞瘤细胞显示出较低的增殖，产生了超氧自由基，诱导了SOD1聚集并降低了其活性。由于SOD1在消除ROS物种中的作用及其在ALS中的相关性，我们使用野生型pLG72及其与精神分裂症易感性相关的R30K变异体评估了pLG72和SOD1之间的联系。重组蛋白的体外研究排除了稳定复合物的建立，pLG72可能影响SOD1活性和稳定性。在细胞水平上，胶质母细胞瘤U87细胞中pLG72的异位表达不会影响细胞活力和ROS /超氧化物的产生：在表达R30K pLG72变体的细胞中，仅胱天蛋白酶活性（凋亡的标志物）略有增加。SOD1和pLG72在转染的U87胶质母细胞瘤细胞中不共定位：pLG72主要定位于线粒体标记，而SOD1主要在胞质中。此外，pLG72的异位表达似乎不会改变SOD1的表达及其聚集。总之，生化和细胞研究的结合可以排除pLG72调节SOD1功能和聚集，因此它可能在ALS易感性中起作用。