Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 10;13(10):1216.
doi: 10.3390/antiox13101216.

PON1 and PON3 in Alzheimer's Disease: Similar Functions but Different Roles

Alessandro Trentini  1 , Valentina Rosta  1 , Raffaella Riccetti  1 , Gianmarco Mola  2 , Riccardo Galletti  2 , Marco Pinotti  2 , Vincenza Senia  2 , Giovanni Zuliani  2 , Carlo Cervellati  2
Affiliations

PON1 and PON3 in Alzheimer's Disease: Similar Functions but Different Roles

Alessandro Trentini et al. Antioxidants (Basel). .

Abstract

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 (p < 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, p < 0.0001) and MPO activity (r = 0.264, p < 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.

Keywords: Alzheimer’s disease; high-density lipoprotein; mild cognitive impairment; paraoxonase.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Scatter plot for the analysis of the correlation between serum PON3 concentration and serum arylesterase activity.
Figure 2
Figure 2
Serum levels of PON3 protein concentration (A) and arylesterase activity (B) in Controls, MCI and AD. Abbreviations: MCI, Mild Cognitive Impairment; AD, Alzheimer’s disease.
Figure 3
Figure 3
Serum PON3 protein concentration (A) and serum arylesterase activity (B) in individuals with and without brain atrophy.
Figure 4
Figure 4
Scatter plot for the analysis of correlation between HDL-C and serum PON3 (A) and between serum HDL-C and serum arylesterase activity (B).
Figure 5
Figure 5
Scatter plot for the analysis of correlation between serum MPO protein concentration and serum PON3 (A) and between serum MPO protein concentration and serum arylesterase activity (B).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Teiber J.F., Draganov D.I., Du B.N. Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3. Biochem. Pharmacol. 2003;66:887–896. doi: 10.1016/S0006-2952(03)00401-5. - DOI - PubMed
    1. Draganov D.I., Stetson P.L., Watson C.E., Billecke S.S., La Du B.N. Rabbit Serum Paraoxonase 3 (PON3) Is a High Density Lipoprotein-associated Lactonase and Protects Low Density Lipoprotein against Oxidation. J. Biol. Chem. 2000;275:33435–33442. doi: 10.1074/jbc.M004543200. - DOI - PubMed
    1. Draganov D.I., Teiber J.F., Speelman A., Osawa Y., Sunahara R., La Du B.N. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J. Lipid Res. 2005;46:1239–1247. doi: 10.1194/jlr.M400511-JLR200. - DOI - PubMed
    1. Furlong C.E., Marsillach J., Jarvik G.P., Costa L.G. Paraoxonases-1, -2 and -3: What are their functions? Chem. Biol. Interact. 2016;259:51–62. doi: 10.1016/j.cbi.2016.05.036. - DOI - PMC - PubMed
    1. Cervellati C., Valacchi G., Tisato V., Zuliani G., Marsillach J. Evaluating the link between Paraoxonase-1 levels and Alzheimer’s disease development. Minerva Medica. 2019;110:238–250. doi: 10.23736/S0026-4806.18.05875-5. - DOI - PMC - PubMed

LinkOut - more resources