Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects

• Published in: Neurobiology of disease Vol. 196; p. 106505
• Main Authors: Tong, Bin, Ba, Yaoqi, Li, Zhengyang, Yang, Caidi, Su, Kangtai, Qi, Haodong, Zhang, Deju, Liu, Xiao, Wu, Yuting, Chen, Yixuan, Ling, Jitao, Zhang, Jing, Yin, Xiaoping, Yu, Peng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2024; Elsevier
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; ApoE; Humans; Lipid metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - physiology; Mitochondria; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson's disease; PPARs; Mitochondria; ApoE; Parkinson's disease; Lipid metabolism; Alzheimer's disease; PPARs
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2024.106505

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders. •This paper reviews the role of lipid metabolism in the occurrence and development of Alzheimer's disease and Parkinson's disease and demonstrates the potential of developing relevant therapeutic strategies based on lipid metabolism as a breakthrough point.•We updated the mechanisms of the involvement of lipid metabolism in the pathogenesis of AD and PD and clarified the theoretical basis of the involvement of lipid metabolism in disease.•This paper reviews the application of lipid monitoring in AD and PD.•In this paper, we summarize the current treatment methods and the latest research progress for specific lipid metabolism pathways and confirm the possibility of clinical treatment.