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Advanced Neurology

REVIEW ARTICLE
Lipid metabolism dysregulation in Parkinson’s

disease: Mechanistic insights and therapeutic
implications

Ming-Ming Wang 1,2† , Xiao-Min Wen 2,3† , Hui Dong 4,5 , Xue-Qin Song 4,5 ,
2,3
2,3
Sheng-Xi Wu * , and Ye Xi *
1 The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University,
Shijiazhuang, Hebei, China
2 Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an,
Shaanxi, China
3 The Shaanxi Province Key Laboratory of Brain Function Analysis and Modulation, Xi’an, Shaanxi, China
4 Key Laboratory of Clinical Neurology, Ministry of Education, Hebei Medical University, Shijiazhuang,
Hebei, China
5 Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

Abstract
† These authors contributed equally
to this work.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by
*Corresponding authors: the selective degeneration of nigrostriatal dopaminergic neurons and pathological
Sheng-Xi Wu accumulation of α-synuclein (α-Syn) aggregates. Emerging evidence indicates the
(shengxi@fmmu.edu.cn);
Ye Xi important role of lipid metabolism dysregulation in driving these pathological
(ye.xi@fmmu.edu.cn) features. As major structural components of brain tissue and critical regulators of
neuronal function, lipids are involved in diverse biological processes, including cell
Citation: Wang M, Wen X,
Dong H, Song X, Wu S, Xi Y. membrane formation, intercellular signaling, energy storage, and homeostasis.
Lipid metabolism dysregulation in Their dysregulation directly affects neural functions, such as synaptic transmission,
Parkinson’s disease: Mechanistic antioxidant defense, and inflammatory modulation. PD is recognized not only as
insights and therapeutic a “proteinopathy” but also as an “organelle communication disorder,” involving
implications. Adv Neurol.
2025;4(4):31-47. dysfunction of membrane contact sites across mitochondria, endoplasmic reticulum,
doi: 10.36922/AN025320086 lysosomes, and lipid droplets (LDs)—a process that may constitute an early pathogenic
event. It is noteworthy that several proteins mediating LDs–organelle contacts are
Received: August 8, 2025
disease-related factors encoded by mutated genes in inherited neurological and
Revised: September 4, 2025 metabolic disorders. Despite the extensive communication between intracellular LDs
Accepted: September 5, 2025 and other organelles through these contact sites, the systematic integration of lipid
metabolism dysregulation into core PD pathogenesis remains elusive. This review
Published online: October 16,
2025 provides a comprehensive overview of the mechanisms underlying lipid–organelle
interactions in PD pathogenesis, with a specific focus on the triangular interplay
Copyright: © 2025 Author(s). among the three core pathological hallmarks: α-Syn aggregation, mitochondrial
This is an Open-Access article
distributed under the terms of the dysfunction, and neuroinflammation, and their convergence with the lipid metabolic
Creative Commons Attribution network. By analyzing molecular mechanisms and clinical implications, with particular
License, permitting distribution, focus on lipid-related biomarkers and therapeutic strategies targeting organelle
and reproduction in any medium, communication pathways, this review aims to provide new insights into the role of
provided the original work is
properly cited. lipid dyshomeostasis in PD pathogenesis and identify feasible therapeutic targets.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Parkinson’s disease; Lipid metabolism; Organelle communication;
regard to jurisdictional claims in
published maps and institutional α-Synuclein; Mitochondrial dysfunction
affiliations.

Volume 4 Issue 4 (2025) 31 doi: 10.36922/AN025320086