"Structural and Metabolic Reprogramming by Docosahexaenoic Acid in Neuronal Cell Models of Alzheimer's Disease"

Docosahexaenoic acid (DHA; 22:6n-3) is the most abundant omega-3 polyunsaturated fatty acid in the mammalian brain and an essential structural component of neuronal membranes. Several research studies indicate that DHA plays critical roles in maintaining membrane lipid composition, synaptic integrity, mitochondrial function, and metabolic homeostasis, processes that are disrupted in Alzheimer's disease (AD) and other neurodegenerative disorders. Because brain DHA availability depends largely on systemic metabolism and liver-brain communication, alterations in DHA homeostasis have been proposed as contributing factors to AD pathogenesis. In vitro neuronal culture models have been pivotal in investigating the molecular and biochemical mechanisms underlying DHA-mediated neuroprotection under disease-related conditions. This mini review summarizes how DHA treatment modulates cellular membrane organisation, synaptogenesis and cytoskeletal integrity, and its neuroprotective role in in vitro neuronal models of AD. Collectively, the literature supports DHA as a key modulator of the structure and metabolic mechanisms at the cellular level and supports the hypothesis that its greatest benefit may occur as a preventive or early-stage intervention. Although effective therapeutic interventions are still lacking, and more investigations integrating next-generation cellular models are still needed, these models provide crucial insights for developing targeted therapeutic applications in AD.