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Title: | LPS-induced mitochondrial dysfunction regulates innate immunity activation and α-synuclein oligomerization in Parkinson's disease | Authors: | Esteves, A. Raquel Silva, Diana F. F. Banha, Diogo Candeias, Emanuel Guedes, Beatriz Cardoso, Sandra M. |
Keywords: | Parkinson’s disease; Lipopolysaccharides; Mitochondrial dysfunction; Innate immunity activation; α-synuclein oligomerization | Issue Date: | Jul-2023 | Publisher: | Elsevier | Project: | PTDC/MED-NEU/3644/2020 UIDB/04539/2020 UIDP/04539/2020 LA/P/0058/2020 |
metadata.degois.publication.title: | Redox Biology | metadata.degois.publication.volume: | 63 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/112392 | ISSN: | 22132317 | DOI: | 10.1016/j.redox.2023.102714 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais I&D CIBB - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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