LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease
Sporadic Parkinson's disease (sPD) is a complex multifactorial disorder which etiology remains elusive. Several mechanisms have been described to contribute to PD development namely mitochondrial dysfunction, activation of inflammatory pathways and the deposition of unfolded proteins such as α-...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723001155 |
| _version_ | 1827934026519805952 |
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| author | A. Raquel Esteves Diana F. Silva Diogo Banha Emanuel Candeias Beatriz Guedes Sandra M. Cardoso |
| author_facet | A. Raquel Esteves Diana F. Silva Diogo Banha Emanuel Candeias Beatriz Guedes Sandra M. Cardoso |
| author_sort | A. Raquel Esteves |
| collection | DOAJ |
| description | Sporadic Parkinson's disease (sPD) is a complex multifactorial disorder which etiology remains elusive. Several mechanisms have been described to contribute to PD development namely mitochondrial dysfunction, activation of inflammatory pathways and the deposition of unfolded proteins such as α-synuclein. Our work shows for the first time that lipopolysaccharide (LPS)-induced activation of innate immunity requires a functional mitochondria and mimics PD pathology in cells. We found in primary mesencephalic neurons that LPS targeted the mitochondria and activated neuronal innate immune responses, which culminated with α-synuclein oligomerization. Moreover, in cybrid cell lines repopulated with mtDNA from sPD subjects with inherent mitochondrial dysfunction and NT2-Rho0 obtained by long-term ethidium bromide exposure, and so without a functional mitochondrial, LPS was not able to further activate innate immunity or increase α-synuclein aggregation.Herein, we showed that mesencephalic neurons are able to activate innate immunity after LPS exposure and this pathway is dependent on mitochondria. Moreover, we disclose that α-synuclein over production is an innate immune response. Our data indicate that mitochondria provide the base for innate immunity activation in idiopathic PD. |
| first_indexed | 2024-03-13T07:32:47Z |
| format | Article |
| id | doaj.art-afa23a29705d44608f9f7c94050897eb |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-03-13T07:32:47Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-afa23a29705d44608f9f7c94050897eb2023-06-04T04:23:43ZengElsevierRedox Biology2213-23172023-07-0163102714LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's diseaseA. Raquel Esteves0Diana F. Silva1Diogo Banha2Emanuel Candeias3Beatriz Guedes4Sandra M. Cardoso5CNC–Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; IIIUC-Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; IIIUC-Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; IIIUC-Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute of Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Corresponding author. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517, Coimbra, Portugal.Sporadic Parkinson's disease (sPD) is a complex multifactorial disorder which etiology remains elusive. Several mechanisms have been described to contribute to PD development namely mitochondrial dysfunction, activation of inflammatory pathways and the deposition of unfolded proteins such as α-synuclein. Our work shows for the first time that lipopolysaccharide (LPS)-induced activation of innate immunity requires a functional mitochondria and mimics PD pathology in cells. We found in primary mesencephalic neurons that LPS targeted the mitochondria and activated neuronal innate immune responses, which culminated with α-synuclein oligomerization. Moreover, in cybrid cell lines repopulated with mtDNA from sPD subjects with inherent mitochondrial dysfunction and NT2-Rho0 obtained by long-term ethidium bromide exposure, and so without a functional mitochondrial, LPS was not able to further activate innate immunity or increase α-synuclein aggregation.Herein, we showed that mesencephalic neurons are able to activate innate immunity after LPS exposure and this pathway is dependent on mitochondria. Moreover, we disclose that α-synuclein over production is an innate immune response. Our data indicate that mitochondria provide the base for innate immunity activation in idiopathic PD.http://www.sciencedirect.com/science/article/pii/S2213231723001155Parkinson's diseaseLipopolysaccharidesMitochondrial dysfunctionInnate immunity activationα-synuclein oligomerization |
| spellingShingle | A. Raquel Esteves Diana F. Silva Diogo Banha Emanuel Candeias Beatriz Guedes Sandra M. Cardoso LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease Redox Biology Parkinson's disease Lipopolysaccharides Mitochondrial dysfunction Innate immunity activation α-synuclein oligomerization |
| title | LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease |
| title_full | LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease |
| title_fullStr | LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease |
| title_full_unstemmed | LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease |
| title_short | LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease |
| title_sort | lps induced mitochondrial dysfunction regulates innate immunity activation and α synuclein oligomerization in parkinson s disease |
| topic | Parkinson's disease Lipopolysaccharides Mitochondrial dysfunction Innate immunity activation α-synuclein oligomerization |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723001155 |
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