The neurobiology of fatty acids: Metabolism, signaling, and roles in neurodegenerative diseases

In the last few years, fatty acids have gained increasing recognition as key modulators of neurodegenerative disease onset and progression. As the fundamental building blocks of most lipids, they not only maintain membrane structure but also support diverse cellular functions. In this review, we summarize their biochemical structures and major classifications, and we describe the pathways governing their synthesis, uptake, and trafficking in the brain. We further explore how fatty acids influence electrophysiological processes by modulating membrane channel conductance, ion-channel-gating, and receptor-mediated signaling, thereby impacting synaptic transmission and cognition performance. Finally, we examine evidence linking fatty acid dynamics in neurodegenerative pathophysiology, highlighting their dual role as both protective and detrimental agents in brain health.