miR-137-5p-Loaded Milk-Derived Small Extracellular Vesicles Modulate Oxidative Stress, Mitochondrial Dysfunction, and...

Area of Science:

• Neuroscience
• Biotechnology
• Molecular Biology

Background:

• Alzheimer's disease (AD) involves complex mechanisms like oxidative stress, neuroinflammation, and protein aggregation.
• MicroRNAs (miRNAs) regulate these pathways, but delivery is challenging.
• Small extracellular vesicles (sEVs) offer a promising solution for miRNA delivery.

Purpose of the Study:

• To investigate the therapeutic potential of milk-derived sEVs loaded with microRNA-137-5p (miR-137-5p) in an in vitro Alzheimer's disease model.
• To evaluate the multi-target modulation effects of these engineered sEVs on AD-related cellular pathology.

Main Methods:

• Milk-derived sEVs were isolated, characterized, and loaded with miR-137-5p.
• An amyloid-beta (Aβ)-induced AD model using SH-SY5Y cells was established.
• Various markers of oxidative stress, inflammation, cytoskeletal damage, mitochondrial function, synaptic integrity, and AD biomarkers (tau, Aβ) were assessed.

Main Results:

• Aβ exposure induced significant oxidative stress, inflammation, mitochondrial dysfunction, and synaptic alterations.
• Treatment with miR-137-5p-loaded sEVs demonstrated a consistent normalization of multiple pathological markers towards control levels.
• Unloaded sEVs showed partial modulation, while loaded sEVs exhibited more comprehensive therapeutic effects.

Conclusions:

• miR-137-5p-enriched sEVs show potential as an experimental platform for multi-target modulation of Alzheimer's disease cellular pathology.
• These findings highlight the promise of engineered sEVs for AD therapeutics.
• Further in vivo studies are necessary to confirm translational relevance.