Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease
In recent years progress in molecular biology and genetics have advanced our understanding of neurological disorders and highlighted synergistic relationships with inflammatory and age-related processes. Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterized by loss of...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122001139 |
| _version_ | 1811252260660838400 |
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| author | Adamantios Mamais Alice Kaganovich Kirsten Harvey |
| author_facet | Adamantios Mamais Alice Kaganovich Kirsten Harvey |
| author_sort | Adamantios Mamais |
| collection | DOAJ |
| description | In recent years progress in molecular biology and genetics have advanced our understanding of neurological disorders and highlighted synergistic relationships with inflammatory and age-related processes. Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Increasing extensive evidence supports the contribution of genetic risk variants and inflammation in the pathobiology of this disease. Functional and genetic studies demonstrate an overlap between genes linked to increased risk for PD and autoimmune diseases. Variants identified in loci adjacent to LRRK2, GBA, and HLA establish a crosstalk between the pathobiologies of the two disease spectra. Furthermore, common signalling pathways associated with the pathogenesis of genetic PD are also relevant to inflammatory signaling include MAPK, NF-κB, Wnt and inflammasome signaling. Importantly, post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines. In this review we will focus on the principal mechanisms of genetic, inflammatory and age-related risk that intersect in the pathogenesis of PD. |
| first_indexed | 2024-04-12T16:32:09Z |
| format | Article |
| id | doaj.art-9b9ef845038a469aaabe13b76784398c |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-12T16:32:09Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-9b9ef845038a469aaabe13b76784398c2022-12-22T03:25:07ZengElsevierNeurobiology of Disease1095-953X2022-07-01169105721Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s diseaseAdamantios Mamais0Alice Kaganovich1Kirsten Harvey2Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL, USALaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USADepartment of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.; Corresponding author.In recent years progress in molecular biology and genetics have advanced our understanding of neurological disorders and highlighted synergistic relationships with inflammatory and age-related processes. Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Increasing extensive evidence supports the contribution of genetic risk variants and inflammation in the pathobiology of this disease. Functional and genetic studies demonstrate an overlap between genes linked to increased risk for PD and autoimmune diseases. Variants identified in loci adjacent to LRRK2, GBA, and HLA establish a crosstalk between the pathobiologies of the two disease spectra. Furthermore, common signalling pathways associated with the pathogenesis of genetic PD are also relevant to inflammatory signaling include MAPK, NF-κB, Wnt and inflammasome signaling. Importantly, post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines. In this review we will focus on the principal mechanisms of genetic, inflammatory and age-related risk that intersect in the pathogenesis of PD.http://www.sciencedirect.com/science/article/pii/S0969996122001139Parkinson's diseaseGeneticsCell signalling pathwaysInflammationAging |
| spellingShingle | Adamantios Mamais Alice Kaganovich Kirsten Harvey Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease Neurobiology of Disease Parkinson's disease Genetics Cell signalling pathways Inflammation Aging |
| title | Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease |
| title_full | Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease |
| title_fullStr | Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease |
| title_full_unstemmed | Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease |
| title_short | Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson’s disease |
| title_sort | convergence of signalling pathways in innate immune responses and genetic forms of parkinson s disease |
| topic | Parkinson's disease Genetics Cell signalling pathways Inflammation Aging |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122001139 |
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