Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis
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Published on: February 28, 2021
Jofre Tenorio-Laranga1, Francisco Coret-Ferrer, Buenaventura Casanova-Estruch
1Department of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Background:
Multiple sclerosis (MS) is a complex, inflammatory and neurodegenerative disease of the central nervous system leading to long-term disability. Recent studies indicate a close association between inflammation and neurodegeneration in all lesions and disease stages of MS. Prolyl oligopeptidase (POP) is a proline-specific serine protease that cleaves several neuroactive peptides. This peptidase has been implicated in neurodegeneration, as well as in the modulation of the inflammatory response.
Methods:
We examined plasma POP and the levels of an endogenous POP inhibitor from relapsing remitting MS patients and compared these with healthy controls, by monitoring the fluorescent changes due to standard fluorescently labelled substrate cleavage. We analysed the data in relationship to patient age and disease disability status.
Results:
We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor. The POP activity was also correlated with patient age and disability status. The lowered POP activity from plasma of MS patients could be rescued by reductants
Conclusions:
The decrease in circulating POP activity measured in MS is reverted by reductants. This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients. Plasma levels of POP activity as well as those of their endogenous inhibitor are suggested as biomarkers of inflammation and oxidative stress in MS.
Insights
Plasma prolyl oligopeptidase (POP) activity is decreased in multiple sclerosis (MS) patients due to oxidative stress. This finding suggests POP activity and its inhibitor levels may serve as biomarkers for MS inflammation and oxidative stress.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative central nervous system disease.
- Inflammation and neurodegeneration are closely linked in MS lesions and disease progression.
- Prolyl oligopeptidase (POP) is a protease involved in neurodegeneration and inflammation modulation.
Purpose of the Study:
- To investigate plasma prolyl oligopeptidase (POP) activity and its endogenous inhibitor levels in relapsing-remitting MS patients.
- To correlate POP activity with patient age and disease disability status.
- To explore the role of oxidative conditions in POP inactivation in MS.
Main Methods:
- Measured plasma POP activity using fluorescently labeled substrates in MS patients and healthy controls.
- Quantified levels of endogenous POP inhibitors.
- Analyzed data in relation to patient age and disability scores.
Main Results:
- Observed significantly lower POP activity in MS patients compared to controls.
- Found increased levels of the endogenous POP inhibitor in MS patients.
- Demonstrated that reduced POP activity in MS plasma could be restored by reductants.
Conclusions:
- Decreased POP activity in MS is linked to oxidative plasma conditions.
- POP inactivation in MS plasma may be caused by prevailing oxidative stress.
- Plasma POP activity and inhibitor levels show potential as biomarkers for inflammation and oxidative stress in MS.
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