Multiple sclerosis (MS) is a debilitating neurological disorder involving concurrent immune-mediated demyelination and progressive neurodegeneration. Although disease-modifying therapies (DMTs) effect Show more
Multiple sclerosis (MS) is a debilitating neurological disorder involving concurrent immune-mediated demyelination and progressive neurodegeneration. Although disease-modifying therapies (DMTs) effectively modulate peripheral immune responses and reduce relapse rates, they are ineffective at halting disease progression and promoting central nervous system (CNS) repair. This review outlines a new therapeutic approach that targets two important microRNAs: miR-219, which stimulates oligodendrogenesis and remyelination, and miR-146a, which regulates innate immune responses and neuroinflammation. We present compelling evidence showing that the dysregulation of these microRNAs establishes a cycle of inflammatory damage and regenerative failure in chronic MS lesions. Preclinical models show that supplementing with miR-219 drives oligodendrocyte precursor cell (OPC) differentiation and myelin restoration by repressing critical inhibitors, such as PDGFRα and LINGO-1. Concurrently, miR-146a modulates neuroinflammatory cascades by regulating the NF-κB pathway, promoting the polarization of microglia toward a protective M2 phenotype, and enhancing OPC maturation. Despite its therapeutic potential, there are significant challenges to its translation, including optimizing CNS-targeted delivery systems, navigating microRNA pleiotropy, and establishing biomarker-driven treatment paradigms. We propose that a dual-targeting approach leveraging advanced nanocarriers for spatiotemporal microRNA delivery represents a transformative frontier in MS therapeutics, potentially bridging the critical gap between immunomodulation and genuine neurorestoration. Show less
Polymorphisms in the melanocortin 4 receptor (MC4R) gene with occurrence and progression of chronic diseases such as obesity and cardiovascular disease (CVD) have long been addressed but there is a la Show more
Polymorphisms in the melanocortin 4 receptor (MC4R) gene with occurrence and progression of chronic diseases such as obesity and cardiovascular disease (CVD) have long been addressed but there is a lack of evidence for complex interrelationships, including direct and indirect effects of these variables. This review specifically focuses on studying the effects of healthy diet interaction and MC4R polymorphisms on the development of CVD. The quantity and quality of carbohydrates and proteins consumed are related to obesity susceptibility and cardiometabolic risk factors. A healthy dietary pattern such as a Mediterranean dietary can modulate the association between MC4R polymorphisms (rs17782313) and the risk of CVDs. Also, the Nordic diet can reduce lipid profiles such as low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. On the other hand, MC4R interaction with the dietary inflammatory index decreases high-density lipoprotein cholesterol levels and increases LDL-C and triglyceride (TG) levels. Additionally, the DASH diet decreases TG, atherogenic index of plasma, systolic blood pressure, diastolic blood pressure, and serum glucose. The interaction between MC4R genes and diets plays an important role in the development of CVD. Adherence to healthy diets such as the Mediterranean, Nordic, Anti-inflammatory, and Dash diets might be an efficient strategy to prevent CVD. The potential for personalized diets to be developed for the treatment and prevention of CVD and its related comorbidities is expected to expand as this field develops. Show less