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Extracellular Purine Metabolism-Potential Target in Multiple Sclerosis.
Danijela Laketa1, Irena Lavrnja2
1Department of General Physiology and Biophysics, Institute for Physiology and Biochemistry "Ivan Djaja", Faculty of Biology, University of Belgrade, Studentski Trg 3, Belgrade, Republic of Serbia. danijela@bio.bg.ac.rs.
Molecular Neurobiology
|March 19, 2024
Summary
The purinergic system impacts multiple sclerosis (MS) pathogenesis. Targeting adenosine signaling and specific receptors like P2Y12 offers potential therapeutic strategies for neuroinflammation in MS.
Area of Science:
- Neuroimmunology
- Molecular Biology
Background:
- Multiple sclerosis (MS) is a heterogeneous neuroinflammatory and neurodegenerative disease.
- The purinergic signaling system, involving extracellular purines and enzymes, plays a critical role in MS pathogenesis.
- Alterations in purinergic signaling components are observed in immune and central nervous system cells in MS and its animal model, experimental autoimmune encephalomyelitis (EAE).
Purpose of the Study:
- To investigate the role of the purinergic signaling system in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).
- To identify potential therapeutic targets within the purinergic system for managing neuroinflammation in MS.
Main Methods:
- Analysis of purinergic signaling components in peripheral immune cells and central nervous system (CNS) glial cells from MS patients and EAE models.
- Assessment of extracellular nucleotide and nucleoside levels.
- Evaluation of ectonucleotidase activity (CD39/CD73).
- Investigation of adenosine receptor (A2A) roles and genetic associations (adenosine deaminase).
- Exploration of novel targets such as P2Y12 receptors and NTPDase2.
Main Results:
- Decreased extracellular ATP and increased adenosine/inosine indicate a shift towards an anti-inflammatory environment in MS.
- Upregulation of CD39/CD73 ectonucleotidases observed in blood and CNS of MS patients.
- Adenosine signaling pathways show promise as therapeutic targets, with beneficial effects of inosine in EAE.
- ADP-dependent P2Y12 receptors and NTPDase2 identified as novel potential targets in MS.
Conclusions:
- The purinergic signaling system is significantly altered in MS and EAE, contributing to disease pathogenesis.
- The adenosinergic system, particularly adenosine receptors, represents a promising target for neuroinflammation treatment.
- Novel targets including P2Y12 receptors and NTPDase2 warrant further investigation for MS therapeutics.
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