Dietary Lipids and Lipid-Mediated Signaling Neurovascular Unit Dysfunction: Implications for Alzheimer's and Parkinson's Diseases Pathogenesis.

Dysregulated lipid homeostasis is closely related to the occurrence and development of various neurological diseases, with the principal mechanism being the damage to the neurovascular unit (NVU). The NVU consists of neurons, vascular endothelial cells, pericytes, astrocytes, and microglia, which integrates glial-vascular-neuronal tripartite communication through tight junction-regulated molecular trafficking. The tripartite communication among these components is essential for cerebrovascular hemodynamic homeostasis and neural signal transmission. Abnormal lipid-mediated signaling impairs the NVU via oxidative stress, inflammatory responses, endothelial cell dysfunction, blood-brain barrier (BBB) disruption, neurotransmitter imbalance, and mitochondrial dysfunction, leading to neuronal dysfunction, death, and thereby contributing to neurological diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). This review systematically examines the influence of diverse lipid species on neurodegenerative diseases, with particular focus on AD and PD, while elucidating their molecular mechanisms in NVU dysfunction. A more in-depth summary on the influence of nutritional factors on the NVU provides a theoretical framework for elucidating the pathogenesis of neurological diseases and developing novel therapeutic strategies.