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Advanced Neurology

REVIEW ARTICLE
Lipid droplets in neurodegenerative disorders:

Molecular insights and therapeutic intervention

†
†
Xin-Yi Chen , Ting-ting Fu , Ling Huang*, and Wan-Di Xiong*
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical
Sciences, Hainan University, Haikou, China

Abstract
Lipid droplets (LDs) are dynamic lipid storage organelles, derived from phospholipid
monolayer membrane of the endoplasmic reticulum. LDs are composed of neutral
lipids, mainly including triglycerides, sterol esters, and other non-polar lipids like
cholesterol. The functions of LDs differ from different cell types in the central nervous
system. The major role of LDs is to maintain lipid homeostasis, provide energy supply,
and play a protective role in response to intracellular oxidative stress in the brain.
Oxidative stress can lead to lipid dyshomeostasis, particularly the accumulation of
LDs, followed by abnormal myelination, neuroinflammation, and cognitive decline.
Neuroinflammation, aging, and age-related neurodegenerative disorders (NDDs) are
† These authors contributed equally
to this work. characterized by the excessive accumulation of LDs in the brain. Although the LDs
accumulation in the brain of the NDDs mouse model has been reported as early as
*Corresponding authors:
Wan-di Xiong a century ago, the role of LDs in the brain remains largely unknown. It is still unclear
(xiongwandi@hainanu.edu.cn) regarding the involvement of LDs accumulation in the pathogenesis of NDDs. In this
Ling Huang review, we provide an overview of LDs biogenesis, the characteristics and functions of
(linghuang@hainanu.edu.cn) LDs from a cell-type perspective, and the pathological roles of LDs in NDDs on recent
Citation: Chen X, Fu T, Huang L, advances. In addition, we discuss the emerging LDs-based therapeutic strategies for
Xiong W. Lipid droplets in NDDs, which may provide promising clues to develop novel therapeutic approaches
neurodegenerative disorders:
Molecular insights and therapeutic for NDDs.
intervention. Adv Neurol.
2025;4(2):1-11.
doi: 10.36922/an.5060 Keywords: Lipid droplets; Neurodegenerative disorders; Aging; Neuroinflammation;
Received: October 7, 2024 Neuroglia
Revised: November 7, 2024
Accepted: November 25, 2024
Published online: December 12, 1. Introduction
2024 Lipid droplets (LDs) serve as dynamic organelles for the storage of neutral lipids,
Copyright: © 2024 Author(s). which play critical roles in the regulation of cellular lipid metabolism, homeostasis,
This is an Open-Access article and energy utilization. In central nervous system (CNS), highly energy-demanding
distributed under the terms of the
Creative Commons Attribution neurons and glial cells are heavily reliant on lipid metabolism, which can provide
License, permitting distribution, nutrition, metabolism, and immunoregulation to neural networks. Although lipids
and reproduction in any medium,
provided the original work is represent around 50% of the dry weight in CNS, the brain has a limited capacity for
properly cited. the storage and oxidation for lipid metabolism. Lipid dyshomeostasis is associated with
1
Publisher’s Note: AccScience neuroinflammation, brain aging, and neurodegenerative disorders (NDDs). LDs, as the
Publishing remains neutral with neutral lipid storage organelles derived from endoplasmic reticulum (ER), are distributed
regard to jurisdictional claims in
published maps and institutional in various cell types, including neurons, microglia, astrocytes, oligodendrocytes, and
affiliations. ependymal cells. LDs show different functions in those cells. Recent advances revealed
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Volume 4 Issue 2 (2025) 1 doi: 10.36922/an.5060