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The Potential Association Between microRNA 135-5P and p62 and Their Effect on NRF2 Pathway in Multiple Sclerosis
Azza Abusree Ahmed1, Salwa Fayez Hasan1, Laila Ahmed Rashed1
1Medical Biochemistry and Molecular Biology Department, Unit of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Background:
Multiple Sclerosis (MS) is a prevalent non-traumatic disabling disease affecting young adults, characterized by complexity in its pathogenesis. Nuclear factor erythroid 2-Related Factor 2 (NRF2) serves as a crucial transcriptional regulator of anti-inflammatory and antioxidant enzymes, influenced by the ubiquitous protein p62. It acts as a scaffold directing substrates to autophagosomes. This study aims to explore the potential association between microRNA 135-5p and p62 and their impact on inflammation and oxidative stress through the NRF2 pathway in MS.
Methods:
The study included 30 healthy controls and 60 MS patients (relapsing-remitting and secondary progressive). Real-time PCR was employed for the detection of Nrf2, p62, miRNA135-5P, and NF-κB in serum, while p53 levels were determined using ELISA.
Results:
Nrf2 and p62 expression was significantly downregulated in the MS group compared to controls. Conversely, miRNA135-5P, NF-κB expression, and P53 levels were significantly elevated in the MS group.
Conclusions:
This study reveals a potential association between miRNA 135-5p and p62, indicating their role in the pathogenesis of MS. Results suggest that miRNA 135-5p and p62 may influence inflammation and oxidative stress in MS through the NRF2 pathway, potentially mediated by NF-κB and p53.
Insights
This study found lower levels of Nuclear factor erythroid 2-Related Factor 2 (NRF2) and p62 in Multiple Sclerosis (MS) patients. Elevated microRNA 135-5p, NF-κB, and p53 suggest their involvement in MS pathogenesis via the NRF2 pathway.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Biochemistry
Background:
- Multiple Sclerosis (MS) is a disabling neurological disease with complex pathogenesis.
- Nuclear factor erythroid 2-Related Factor 2 (NRF2) regulates antioxidant and anti-inflammatory responses.
- p62 acts as a scaffold protein influencing NRF2 activity and autophagy.
Purpose of the Study:
- To investigate the association between microRNA 135-5p and p62 in MS.
- To explore their impact on inflammation and oxidative stress via the NRF2 pathway in MS.
Main Methods:
- Serum samples from 60 MS patients and 30 healthy controls were analyzed.
- Real-time PCR was used to quantify Nrf2, p62, miRNA135-5P, and NF-κB.
- ELISA was employed to measure p53 levels.
Main Results:
- Nrf2 and p62 expression were significantly downregulated in MS patients.
- miRNA135-5P, NF-κB expression, and p53 levels were significantly elevated in MS patients.
- A potential link between miRNA 135-5p and p62 in MS pathogenesis was identified.
Conclusions:
- miRNA 135-5p and p62 may play a role in MS pathogenesis.
- These molecules might influence inflammation and oxidative stress through the NRF2 pathway.
- NF-κB and p53 may mediate the effects of miRNA 135-5p and p62 in MS.
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