Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases

The blood–brain barrier (BBB) is a critical structure that maintains the brain’s homeostasis by regulating the transport of molecules and protecting it from harmful substances. However, in neurological diseases such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis...

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Main Authors: Luo Fu, Ting Luo, Zhongnan Hao, Yongli Pan, Wenqiang Xin, Lin Zhang, Zhuhong Lai, Haitao Zhang, Hua Liu, Wei Wei
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1603292/full
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author Luo Fu
Luo Fu
Ting Luo
Ting Luo
Zhongnan Hao
Yongli Pan
Yongli Pan
Wenqiang Xin
Lin Zhang
Lin Zhang
Zhuhong Lai
Haitao Zhang
Hua Liu
Wei Wei
Wei Wei
author_facet Luo Fu
Luo Fu
Ting Luo
Ting Luo
Zhongnan Hao
Yongli Pan
Yongli Pan
Wenqiang Xin
Lin Zhang
Lin Zhang
Zhuhong Lai
Haitao Zhang
Hua Liu
Wei Wei
Wei Wei
author_sort Luo Fu
collection DOAJ
description The blood–brain barrier (BBB) is a critical structure that maintains the brain’s homeostasis by regulating the transport of molecules and protecting it from harmful substances. However, in neurological diseases such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, the integrity and function of the BBB can be significantly compromised. In these conditions, BBB disruption leads to increased permeability, which facilitates neuroinflammation, exacerbates neuronal damage, and accelerates disease progression. Recent research has highlighted the potential of lipid-based carriers, including liposomes and lipid droplets (LDs), in modulating the BBB’s integrity and function in various neurological diseases. Liposomes, with their ability to cross the BBB via mechanisms such as receptor-mediated transcytosis and carrier-mediated transport, are emerging as promising vehicles for the targeted delivery of therapeutic agents to the brain. These properties allow liposomes to effectively reduce infarct size and promote neuroprotection in ischemic stroke, as well as deliver drugs in the treatment of neurodegenerative diseases. Furthermore, LDs—dynamic regulators of lipid metabolism and cellular energy—play an essential role in maintaining cellular homeostasis, particularly during periods of stress when BBB function is compromised. These LDs help sustain cellular energy needs and modulate inflammatory responses, which are key factors in maintaining BBB integrity. Surface modifications of liposomes can further enhance their targeting efficiency, enabling them to selectively bind to specific brain cell types, including neurons, astrocytes, and microglia. This customization improves the precision of therapeutic delivery and supports the development of more tailored treatments. However, challenges such as immune responses, rapid clearance, and complement activation-related toxicity continue to hinder the broader application of liposomes and LDs in clinical settings. This review will focus on the roles of liposomes and LDs in regulating BBB integrity across a range of neurological diseases, discussing their potential for targeted drug delivery, neuroprotection, and the modulation of neuroinflammation. Additionally, we will explore the strategies being developed to address the limitations that currently restrict their clinical use.
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spelling doaj-art-3b64d9aae5594fb58d4cc9d1e57a772c2025-08-20T03:36:13ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-08-011910.3389/fnins.2025.16032921603292Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseasesLuo Fu0Luo Fu1Ting Luo2Ting Luo3Zhongnan Hao4Yongli Pan5Yongli Pan6Wenqiang Xin7Lin Zhang8Lin Zhang9Zhuhong Lai10Haitao Zhang11Hua Liu12Wei Wei13Wei Wei14Department of Neurology, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Gastrointestinal and Minimally Invasive Surgery, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Neurology, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, Göttingen, Lower Saxony, GermanyDepartment of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, Göttingen, Lower Saxony, GermanyDepartment of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaJiangxi Key Laboratory of Neurological Diseases, Department of Neurosurgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, Göttingen, Lower Saxony, GermanyDepartment of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Mianyang Central Hospital, Mianyang, Sichuan, ChinaDepartment of Neurology, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Neurology, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Neurology, The Affiliated Hospital of Southwest Jiaotong University and The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaDepartment of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, Göttingen, Lower Saxony, GermanyThe blood–brain barrier (BBB) is a critical structure that maintains the brain’s homeostasis by regulating the transport of molecules and protecting it from harmful substances. However, in neurological diseases such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, the integrity and function of the BBB can be significantly compromised. In these conditions, BBB disruption leads to increased permeability, which facilitates neuroinflammation, exacerbates neuronal damage, and accelerates disease progression. Recent research has highlighted the potential of lipid-based carriers, including liposomes and lipid droplets (LDs), in modulating the BBB’s integrity and function in various neurological diseases. Liposomes, with their ability to cross the BBB via mechanisms such as receptor-mediated transcytosis and carrier-mediated transport, are emerging as promising vehicles for the targeted delivery of therapeutic agents to the brain. These properties allow liposomes to effectively reduce infarct size and promote neuroprotection in ischemic stroke, as well as deliver drugs in the treatment of neurodegenerative diseases. Furthermore, LDs—dynamic regulators of lipid metabolism and cellular energy—play an essential role in maintaining cellular homeostasis, particularly during periods of stress when BBB function is compromised. These LDs help sustain cellular energy needs and modulate inflammatory responses, which are key factors in maintaining BBB integrity. Surface modifications of liposomes can further enhance their targeting efficiency, enabling them to selectively bind to specific brain cell types, including neurons, astrocytes, and microglia. This customization improves the precision of therapeutic delivery and supports the development of more tailored treatments. However, challenges such as immune responses, rapid clearance, and complement activation-related toxicity continue to hinder the broader application of liposomes and LDs in clinical settings. This review will focus on the roles of liposomes and LDs in regulating BBB integrity across a range of neurological diseases, discussing their potential for targeted drug delivery, neuroprotection, and the modulation of neuroinflammation. Additionally, we will explore the strategies being developed to address the limitations that currently restrict their clinical use.https://www.frontiersin.org/articles/10.3389/fnins.2025.1603292/fulllipid dropletsliposomesblood–brain barrierneurological disordersneuroprotection
spellingShingle Luo Fu
Luo Fu
Ting Luo
Ting Luo
Zhongnan Hao
Yongli Pan
Yongli Pan
Wenqiang Xin
Lin Zhang
Lin Zhang
Zhuhong Lai
Haitao Zhang
Hua Liu
Wei Wei
Wei Wei
Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases
Frontiers in Neuroscience
lipid droplets
liposomes
blood–brain barrier
neurological disorders
neuroprotection
title Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases
title_full Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases
title_fullStr Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases
title_full_unstemmed Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases
title_short Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood–brain barrier function in neurological diseases
title_sort exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood brain barrier function in neurological diseases
topic lipid droplets
liposomes
blood–brain barrier
neurological disorders
neuroprotection
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1603292/full
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