Trentini Alessandro, Rosta Valentina, Riccetti Raffaella, Mola Gianmarco, Galletti Riccardo, Pinotti Marco, Senia Vincenza, Zuliani Giovanni, Cervellati Carlo
Department of Environmental and Prevention Sciences, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
Department of Translational Medicine and for Romagna, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
Antioxidants (Basel). 2024 Oct 10;13(10):1216. doi: 10.3390/antiox13101216.
Paraoxonase 1 (PON1) and Paraoxonase 3 (PON3) are enzymes located on the surface of high-density lipoprotein (HDL) and share similar antioxidant properties, possibly modulated by other proteins such as Myeloperoxidase (MPO), which drives the shift from functional to dysfunctional HDL. PON1 has been extensively studied in relation to Alzheimer's Disease (AD), but the role of PON3 remains unknown. To fill this knowledge gap, the study analyzed PON3 protein levels and PON1-arylesterase activity in 99 AD patients, 100 patients with mild cognitive impairment (MCI), and 79 cognitively normal controls. The results showed that serum PON3 levels remained unchanged across all groups. In contrast, serum arylesterase activity was significantly reduced in both AD and MCI patients compared to controls ( < 0.001 for both comparisons). Surprisingly, there was no correlation between arylesterase activity and MPO protein concentration or activity. However, PON3 was found to have a significant positive correlation with both MPO concentration (r = 0.507, < 0.0001) and MPO activity (r = 0.264, < 0.01). In conclusion, we demonstrated for the first time that PON1 and PON3 have distinct relationships with AD, with only PON1 showing a decrease in activity in this disease, while PON3 levels remained unchanged. Another noteworthy finding was the selective correlation between PON3 and MPO, which may suggest a preferential physical association of PON3 with dysfunctional HDL.
对氧磷酶1（PON1）和对氧磷酶3（PON3）是位于高密度脂蛋白（HDL）表面的酶，具有相似的抗氧化特性，可能受其他蛋白质如髓过氧化物酶（MPO）的调节，MPO会促使功能性HDL向功能失调性HDL转变。PON1已被广泛研究与阿尔茨海默病（AD）的关系，但PON3的作用仍不清楚。为填补这一知识空白，该研究分析了99例AD患者、100例轻度认知障碍（MCI）患者和79例认知正常对照者的PON3蛋白水平和PON1-芳基酯酶活性。结果显示，所有组的血清PON3水平均未改变。相比之下，与对照组相比，AD和MCI患者的血清芳基酯酶活性均显著降低（两组比较均P<0.001）。令人惊讶的是，芳基酯酶活性与MPO蛋白浓度或活性之间没有相关性。然而，发现PON3与MPO浓度（r = 0.507，P<0.0001）和MPO活性（r = 0.264，P<0.01）均呈显著正相关。总之，我们首次证明PON1和PON3与AD有不同的关系，只有PON1在该疾病中活性降低，而PON3水平保持不变。另一个值得注意的发现是PON3与MPO之间的选择性相关性，这可能表明PON3与功能失调性HDL存在优先的物理关联。
