Molecular and therapeutic approach of specialised pro-resolving mediators in central nervous system diseases

Abstract: Neuroinflammation is a key pathophysiological hallmark across a spectrum of debilitating neurological disorders, contributing significantly to disease progression and disability. This pervasive inflammatory state arises from an imbalance in lipid mediators, a class of bioactive molecules derived from fatty acids that orchestrate both pro- and anti-inflammatory responses. Specialised pro-resolving lipid mediators (SPMs), a subclass of lipid mediators synthesised from omega-3 and omega-6 polyunsaturated fatty acids, play a pivotal role in orchestrating the timely resolution of inflammation. These SPMs, classified into resolvins, protectins, lipoxins, and maresins, actively promote the termination of inflammatory cascades and tissue repair. Recent research has unveiled a compelling link between dysregulated SPM production and the relentless neuroinflammation observed in various central nervous system pathologies, including Alzheimer's disease, amyotrophic lateral sclerosis, epilepsy, multiple sclerosis, and cerebrovascular disease. This crucial finding underscores the potential for SPMs as novel therapeutic targets, paving the way for a paradigm shift in managing neurological disorders. This review delves into the intricate molecular mechanisms of SPMs, their multifaceted roles within the CNS, their implications in neurological disease pathogenesis, and their burgeoning potential as therapeutic targets in neuroinflammation resolution.