Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.

BACKGROUND: Lipids are fundamental components of the central nervous system (CNS) structure and are essential for maintaining physiological homeostasis. Dysregulation of lipid homeostasis is a critical mechanism driving the pathogenesis and progression of classic CNS diseases, including neurodegenerative disorders, traumatic injuries, and cerebrovascular diseases. These metabolic disturbances trigger pathological processes such as abnormal protein aggregation, neuroinflammation, and lipid peroxidation, creating a vicious cycle that exacerbates disease progression. While targeting lipid metabolism offers a novel therapeutic strategy, its clinical translation faces significant hurdles. SCOPE OF REVIEW: This review systematically summarizes the pathological roles and molecular mechanisms of lipid metabolism dysregulation across six representative CNS disorders: Alzheimer's disease (AD), Parkinson's disease (PD), spinal cord injury (SCI), traumatic brain injury (TBI), stroke, and intracerebral hemorrhage (ICH). These conditions were selected to cover a spectrum of pathologies, including protein-aggregation neurodegeneration, posttraumatic secondary injury, and cerebrovascular damage. The article outlines recent advances in therapeutic interventions targeting lipid metabolism and dissects both the shared and disease-specific regulatory mechanisms within the CNS. KEY CHALLENGES: Despite the therapeutic potential, several challenges impede the development of effective lipid-targeting treatments. These include the incompletely defined mechanisms underlying dynamic lipid changes across different disease stages, insufficient efficiency of drug delivery across the blood-brain barrier, and the limited efficacy of single-target interventions. This review addresses these existing hurdles and proposes potential solutions to overcome them. CONCLUSION: Targeting lipid metabolism represents a promising frontier for treating CNS diseases. By providing a comprehensive reference on the metabolic underpinnings of these disorders and addressing current research bottlenecks, this review aims to lay the groundwork for the development of precise, targeted therapeutic strategies in future clinical applications.