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Review
. 2023 Jul:213:115619.
doi: 10.1016/j.bcp.2023.115619. Epub 2023 May 19.

Role of microglial metabolic reprogramming in Parkinson's disease

Zheng-Ping Huang  1 , Shu-Fen Liu  1 , Jian-Long Zhuang  2 , Lin-Yi Li  1 , Mi-Mi Li  1 , Ya-Li Huang  1 , Yan-Hong Chen  3 , Xiang-Rong Chen  4 , Shu Lin  5 , Li-Chao Ye  6 , Chun-Nuan Chen  7
Affiliations
Review

Role of microglial metabolic reprogramming in Parkinson's disease

Zheng-Ping Huang et al. Biochem Pharmacol. 2023 Jul.

Abstract

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Keywords: Metabolic reprogramming; Microglia; Mitochondria; Neuroinflammation; Parkinson's disease; Signaling pathway.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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