The Link of Paraoxonase 1 Activity and Its Polymorphisms in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelinating lesions in the brain, spinal cord, and optic nerve. It predominantly affects young adults, with women being two to three times more likely to develop the condition than men. The exact cause of MS remains unknown, but oxidative stress and lipid peroxidation are considered key factors in its pathogenesis.

Paraoxonase 1 (PON1) is a hydrolytic enzyme synthesized in the liver and carried by high-density lipoproteins (HDL) in the bloodstream. PON1 protects against lipid oxidation and has been linked to the prevention of neurological disorders due to its antioxidant properties. This blog post delves into the findings of a review investigating the association between PON1 activity, its polymorphisms, and the risk of multiple sclerosis.

Background Human serum paraoxonase (PON) consists of three known members: PON1, PON2, and PON3. These enzymes share significant structural similarities and play vital roles in detoxifying organophosphates and protecting against oxidative stress. PON1, in particular, has been the focus of studies due to its activity in the brain and its potential protective effects against neurological disorders like MS.

Key Findings
The review examined studies from various databases, including PubMed, Scopus, and Google Scholar, to understand the role of PON1 and its polymorphisms in MS. Here are the significant findings:

PON1 Activity and MS:
Reduced PON1 Activity: Studies consistently found that PON1 activity is significantly lower in patients with MS compared to healthy individuals. This reduction in PON1 activity is associated with increased oxidative stress and lipid peroxidation, contributing to the pathogenesis of MS.
Inflammatory Cytokines and Oxidative Stress: Both factors negatively impact PON1 activity, further exacerbating the condition.

PON1 Polymorphisms and MS Risk:
PON1-55 and PON1-192 Polymorphisms: These polymorphisms were investigated for their association with MS. The PON1-55M allele in Italians and the PON1-192Q allele in Poles were found to be associated with a higher risk of developing MS.
No Association with Disease Onset or Type: PON1-55 and PON1-192 polymorphisms were not linked to the age of MS onset or its evolutionary type.

Lipid Profile in MS Patients:
Cholesterol Levels: Total cholesterol levels were significantly higher in MS patients compared to healthy controls. However, there were no significant differences in HDL cholesterol and triglycerides between MS patients and controls.

Discussion
The review underscores the importance of PON1 activity in the context of MS. Decreased PON1 activity contributes to increased oxidative stress, a critical factor in MS pathogenesis. Additionally, specific PON1 polymorphisms, such as PON1-55M and PON1-192Q, have been identified as genetic risk factors for MS in certain populations.

The relationship between lipid metabolism and MS is also highlighted, with altered cholesterol levels observed in MS patients. These findings suggest that interventions aimed at increasing PON1 activity or modifying lipid profiles could potentially benefit MS patients.

Conclusion
The review provides valuable insights into the role of PON1 activity and its polymorphisms in MS. Reduced PON1 activity is a consistent finding across studies and is linked to increased oxidative stress in MS patients. Certain PON1 polymorphisms are associated with a higher risk of developing MS, although they do not affect disease onset or type.

Future research should focus on exploring therapeutic strategies to enhance PON1 activity and investigate the potential benefits of lipid-modifying interventions in MS patients. Increasing awareness about the role of PON1 in MS can lead to better understanding and management of the disease.

References:
Salari, N., Rasoulpoor, S., Hosseinian-Far, A., Razazian, N., Mansouri, K., Mohammadi, M., Vaisi-Raygani, A., Jalali, R., & Shabani, S. (2020). Association between serum paraoxonase 1 activity and its polymorphisms with multiple sclerosis: a systematic review. Neurological Sciences, 42, 491–500. DOI:10.1007/s10072-020-04842-3