Lipid rafts: novel therapeutic targets for metabolic, neurodegenerative, oncological, and cardiovascular diseases.

Abstract

Lipid rafts are specialized microdomains within cellular membranes enriched with cholesterol and sphingolipids that play key roles in cellular organization, signaling, and homeostasis. This review highlights their involvement in protein clustering, energy metabolism, oxidative stress responses, inflammation, autophagy, and apoptosis. These findings clarify their influence on signaling, trafficking, and adhesion while interacting with the extracellular matrix, cytoskeleton, and ion channels, making them pivotal in the progression of various diseases. This review further addresses their contributions to immune responses, including autoimmune diseases, chronic inflammation, and cytokine storms. Additionally, their role as entry points for pathogens has been demonstrated, with raft-associated receptors being exploited by viruses and bacteria to increase infectivity and evade immune defenses. Disruptions in lipid raft dynamics are linked to oxidative stress and cellular signaling defects, which contribute to metabolic, neurodegenerative, and cardiovascular diseases. This review underscores their potential as therapeutic targets, discussing innovations such as engineered lipid raft transplantation. Advances in analytical techniques such as mass spectrometry have expanded our understanding of lipid raft composition and dynamics, opening new directions for research. By consolidating the current insights, we highlight the therapeutic potential of lipid rafts and highlight the need for further exploration of their molecular mechanisms.