Review synthesizing evidence that dysregulated dietary lipids and lipid-mediated signaling impair neurovascular unit components—via oxidative stress, inflammation, BBB disruption, mitochondrial and neurotransmitter dysfunction—and linking these mechanisms to Alzheimer's and Parkinson's disease…

Identifies modifiable lipid-related pathways (diet, BBB integrity, inflammation, mitochondrial dysfunction) that are relevant to PD therapeutic discovery and biomarker development, offering translational hypotheses despite being largely conceptual and needing experimental validation.

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.