MiR-142-3p regulates synaptopathy-driven disease progression in multiple sclerosis.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Multiple sclerosis (MS) involves inflammatory synaptopathy, leading to neuronal loss.
• MiR-142-3p is an inflammatory microRNA with roles in both immune and central nervous systems, proposed as a key player in MS pathogenesis.
• Cerebrospinal fluid (CSF) miR-142-3p is investigated as a potential biomarker and therapeutic target in MS.

Purpose of the Study:

• To assess the correlation between CSF miR-142-3p levels and clinical parameters in MS patients.
• To investigate the impact of miR-142-3p on neuronal excitability and its interaction with disease-modifying therapies (DMTs).
• To explore miR-142-3p as a potential prognostic marker and therapeutic target in MS.

Main Methods:

• Analysis of CSF miR-142-3p levels in 151 MS patients.
• Correlation analysis with clinical progression, IL-1β signaling, and synaptic excitability (transcranial magnetic stimulation).
• Assessment of response to dimethyl fumarate (DMF) in patients and in a mouse model (experimental autoimmune encephalomyelitis - EAE).
• Electrophysiological, molecular, and biochemical analyses.

Main Results:

• CSF miR-142-3p levels positively correlated with MS clinical progression, IL-1β signaling, and synaptic excitability.
• Patients with lower miR-142-3p levels showed superior response to DMF treatment.
• DMF treatment ameliorated EAE course in mice, with a greater effect in miR-142 heterozygous mice, indicating a central protective effect and rescue of miR-142-3p-dependent alterations.

Conclusions:

• MiR-142-3p serves as a novel, negative prognostic CSF marker in MS.
• MiR-142-3p is identified as a molecular target of DMF.
• This microRNA holds promise for developing personalized therapies for MS.