Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review
Palmitoylation is a reversible lipid modification regulated by palmitoyl transferases and acyl-protein thioesterases, in which palmitic acid is attached to protein cysteine residues. This modification plays a pivotal role in modulating membrane localization and protein stability, and its dysregulati...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1615001/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849320453129109504 |
|---|---|
| author | Jingjing Liu Shanshan Wang Lei Fan Xin Zhou Sen Zhang Qinglu Wang Panpan Dong Bo Yu |
| author_facet | Jingjing Liu Shanshan Wang Lei Fan Xin Zhou Sen Zhang Qinglu Wang Panpan Dong Bo Yu |
| author_sort | Jingjing Liu |
| collection | DOAJ |
| description | Palmitoylation is a reversible lipid modification regulated by palmitoyl transferases and acyl-protein thioesterases, in which palmitic acid is attached to protein cysteine residues. This modification plays a pivotal role in modulating membrane localization and protein stability, and its dysregulation is closely associated with various neurodegenerative diseases, including Parkinson’s disease (PD). In PD, synaptotagmin-11, encoded by the PD risk gene SYT11, has been shown to reduce physiological α-synuclein (α-syn) tetramer formation while promoting the aggregation-prone monomeric form in a palmitoylation-dependent manner. In the context of PD, inflammation generally precedes the abnormal aggregation of α-syn and the degeneration of dopaminergic neurons (DA). Microglial activation, regarded as an inflammatory state, is facilitated by the palmitoylation-dependent localization of NLRP3 to the trans-Golgi network, which promotes the activation and expression of the NLRP3 inflammasome, leading to DA neuron loss. Additionally, the DJ-1 protein, encoded by the risk gene PARK7, and the dopamine transporter both undergo palmitoylation and may contribute to disease progression. This review summarizes the emerging link between protein palmitoylation and PD pathogenesis. Understanding the dynamic regulatory mechanisms of palmitoylation and depalmitoylation may facilitate the development of targeted therapeutic strategies for PD. |
| format | Article |
| id | doaj-art-d2116e7bbd4543dc91a83db14c84652f |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-d2116e7bbd4543dc91a83db14c84652f2025-08-20T03:50:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16150011615001Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative reviewJingjing Liu0Shanshan Wang1Lei Fan2Xin Zhou3Sen Zhang4Qinglu Wang5Panpan Dong6Bo Yu7Graduate School of Education, Shandong Sport University, Jinan, ChinaDepartment of Neurology, Zibo 148 Hospital, Zibo, Shandong, ChinaDepartment of Rehabilitation, Liuzhou People’s Hospital, Liuzhou, ChinaGraduate School of Education, Shandong Sport University, Jinan, ChinaGraduate School of Education, Shandong Sport University, Jinan, ChinaGraduate School of Education, Shandong Sport University, Jinan, ChinaCollege of Basic Medicine, Qilu Medical University, Zibo, Shandong, ChinaGraduate School of Education, Shandong Sport University, Jinan, ChinaPalmitoylation is a reversible lipid modification regulated by palmitoyl transferases and acyl-protein thioesterases, in which palmitic acid is attached to protein cysteine residues. This modification plays a pivotal role in modulating membrane localization and protein stability, and its dysregulation is closely associated with various neurodegenerative diseases, including Parkinson’s disease (PD). In PD, synaptotagmin-11, encoded by the PD risk gene SYT11, has been shown to reduce physiological α-synuclein (α-syn) tetramer formation while promoting the aggregation-prone monomeric form in a palmitoylation-dependent manner. In the context of PD, inflammation generally precedes the abnormal aggregation of α-syn and the degeneration of dopaminergic neurons (DA). Microglial activation, regarded as an inflammatory state, is facilitated by the palmitoylation-dependent localization of NLRP3 to the trans-Golgi network, which promotes the activation and expression of the NLRP3 inflammasome, leading to DA neuron loss. Additionally, the DJ-1 protein, encoded by the risk gene PARK7, and the dopamine transporter both undergo palmitoylation and may contribute to disease progression. This review summarizes the emerging link between protein palmitoylation and PD pathogenesis. Understanding the dynamic regulatory mechanisms of palmitoylation and depalmitoylation may facilitate the development of targeted therapeutic strategies for PD.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1615001/fullParkinson’s diseasepalmitoylationα-synucleinsynaptotagmin-11NLRP3 inflammasome |
| spellingShingle | Jingjing Liu Shanshan Wang Lei Fan Xin Zhou Sen Zhang Qinglu Wang Panpan Dong Bo Yu Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review Frontiers in Immunology Parkinson’s disease palmitoylation α-synuclein synaptotagmin-11 NLRP3 inflammasome |
| title | Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review |
| title_full | Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review |
| title_fullStr | Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review |
| title_full_unstemmed | Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review |
| title_short | Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson’s disease: a narrative review |
| title_sort | protein regulatory network mediated by palmitoylation modifications in the pathological progression of parkinson s disease a narrative review |
| topic | Parkinson’s disease palmitoylation α-synuclein synaptotagmin-11 NLRP3 inflammasome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1615001/full |
| work_keys_str_mv | AT jingjingliu proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT shanshanwang proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT leifan proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT xinzhou proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT senzhang proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT qingluwang proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT panpandong proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview AT boyu proteinregulatorynetworkmediatedbypalmitoylationmodificationsinthepathologicalprogressionofparkinsonsdiseaseanarrativereview |