Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease
Parkinson's disease (PD) is a movement disorder attributed to the loss of dopaminergic (DA) neurons mainly in the substantia nigra pars compacta. Motor symptoms include resting tremor, rigidity, and bradykinesias, while non-motor symptoms include autonomic dysfunction, anxiety, and sleeping pro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.636139/full |
| _version_ | 1818667246350761984 |
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| author | Albert Frank Magnusen Shelby Loraine Hatton Reena Rani Manoj Kumar Pandey Manoj Kumar Pandey |
| author_facet | Albert Frank Magnusen Shelby Loraine Hatton Reena Rani Manoj Kumar Pandey Manoj Kumar Pandey |
| author_sort | Albert Frank Magnusen |
| collection | DOAJ |
| description | Parkinson's disease (PD) is a movement disorder attributed to the loss of dopaminergic (DA) neurons mainly in the substantia nigra pars compacta. Motor symptoms include resting tremor, rigidity, and bradykinesias, while non-motor symptoms include autonomic dysfunction, anxiety, and sleeping problems. Genetic mutations in a number of genes (e.g., LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7) and the resultant abnormal activation of microglial cells are assumed to be the main reasons for the loss of DA neurons in PD with genetic causes. Additionally, immune cell infiltration and their participation in major histocompatibility complex I (MHCI) and/or MHCII-mediated processing and presentation of cytosolic or mitochondrial antigens activate the microglial cells and cause the massive generation of pro-inflammatory cytokines and chemokines, which are all critical for the propagation of brain inflammation and the neurodegeneration in PD with genetic and idiopathic causes. Despite knowing the involvement of several of such immune devices that trigger neuroinflammation and neurodegeneration in PD, the exact disease mechanism or the innovative biomarker that could detect disease severity in PD linked to LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7 defects is largely unknown. The current review has explored data from genetics, immunology, and in vivo and ex vivo functional studies that demonstrate that certain genetic defects might contribute to microglial cell activation and massive generation of a number of pro-inflammatory cytokines and chemokines, which ultimately drive the brain inflammation and lead to neurodegeneration in PD. Understanding the detailed involvement of a variety of immune mediators, their source, and the target could provide a better understanding of the disease process. This information might be helpful in clinical diagnosis, monitoring of disease progression, and early identification of affected individuals. |
| first_indexed | 2024-12-17T06:17:22Z |
| format | Article |
| id | doaj.art-3b82b8800ced43bc9bd40e2b95c507cf |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-17T06:17:22Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-3b82b8800ced43bc9bd40e2b95c507cf2022-12-21T22:00:28ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-06-011210.3389/fneur.2021.636139636139Genetic Defects and Pro-inflammatory Cytokines in Parkinson's DiseaseAlbert Frank Magnusen0Shelby Loraine Hatton1Reena Rani2Manoj Kumar Pandey3Manoj Kumar Pandey4Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United StatesDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United StatesDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United StatesDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Paediatrics of University of Cincinnati College of Medicine, Cincinnati, OH, United StatesParkinson's disease (PD) is a movement disorder attributed to the loss of dopaminergic (DA) neurons mainly in the substantia nigra pars compacta. Motor symptoms include resting tremor, rigidity, and bradykinesias, while non-motor symptoms include autonomic dysfunction, anxiety, and sleeping problems. Genetic mutations in a number of genes (e.g., LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7) and the resultant abnormal activation of microglial cells are assumed to be the main reasons for the loss of DA neurons in PD with genetic causes. Additionally, immune cell infiltration and their participation in major histocompatibility complex I (MHCI) and/or MHCII-mediated processing and presentation of cytosolic or mitochondrial antigens activate the microglial cells and cause the massive generation of pro-inflammatory cytokines and chemokines, which are all critical for the propagation of brain inflammation and the neurodegeneration in PD with genetic and idiopathic causes. Despite knowing the involvement of several of such immune devices that trigger neuroinflammation and neurodegeneration in PD, the exact disease mechanism or the innovative biomarker that could detect disease severity in PD linked to LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7 defects is largely unknown. The current review has explored data from genetics, immunology, and in vivo and ex vivo functional studies that demonstrate that certain genetic defects might contribute to microglial cell activation and massive generation of a number of pro-inflammatory cytokines and chemokines, which ultimately drive the brain inflammation and lead to neurodegeneration in PD. Understanding the detailed involvement of a variety of immune mediators, their source, and the target could provide a better understanding of the disease process. This information might be helpful in clinical diagnosis, monitoring of disease progression, and early identification of affected individuals.https://www.frontiersin.org/articles/10.3389/fneur.2021.636139/fullneuroimmunologyimmunogeneticsinnate and adaptive immunityglycosphingolipidaggregated proteinsbrain disease |
| spellingShingle | Albert Frank Magnusen Shelby Loraine Hatton Reena Rani Manoj Kumar Pandey Manoj Kumar Pandey Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease Frontiers in Neurology neuroimmunology immunogenetics innate and adaptive immunity glycosphingolipid aggregated proteins brain disease |
| title | Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease |
| title_full | Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease |
| title_fullStr | Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease |
| title_full_unstemmed | Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease |
| title_short | Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease |
| title_sort | genetic defects and pro inflammatory cytokines in parkinson s disease |
| topic | neuroimmunology immunogenetics innate and adaptive immunity glycosphingolipid aggregated proteins brain disease |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.636139/full |
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