--- _id: '10607' abstract: - lang: eng text: The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders. acknowledgement: This study was supported by grants of the Austrian Science Fund (FWF) F4414 and W1206-08. Electron microscopy was performed at the Scientific Service Units (SSU) of IST-Austria through resources provided by the Electron Microscopy Facility. article_processing_charge: No article_type: original author: - first_name: Serena full_name: Venezia, Serena last_name: Venezia - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Gregor K. full_name: Wenning, Gregor K. last_name: Wenning - first_name: Nadia full_name: Stefanova, Nadia last_name: Stefanova citation: ama: Venezia S, Kaufmann W, Wenning GK, Stefanova N. Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson’s disease. Parkinsonism & Related Disorders. 2021;91:59-65. doi:10.1016/j.parkreldis.2021.09.007 apa: Venezia, S., Kaufmann, W., Wenning, G. K., & Stefanova, N. (2021). Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson’s disease. Parkinsonism & Related Disorders. Elsevier. https://doi.org/10.1016/j.parkreldis.2021.09.007 chicago: Venezia, Serena, Walter Kaufmann, Gregor K. Wenning, and Nadia Stefanova. “Toll-like Receptor 4 Deficiency Facilitates α-Synuclein Propagation and Neurodegeneration in a Mouse Model of Prodromal Parkinson’s Disease.” Parkinsonism & Related Disorders. Elsevier, 2021. https://doi.org/10.1016/j.parkreldis.2021.09.007. ieee: S. Venezia, W. Kaufmann, G. K. Wenning, and N. Stefanova, “Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson’s disease,” Parkinsonism & Related Disorders, vol. 91. Elsevier, pp. 59–65, 2021. ista: Venezia S, Kaufmann W, Wenning GK, Stefanova N. 2021. Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson’s disease. Parkinsonism & Related Disorders. 91, 59–65. mla: Venezia, Serena, et al. “Toll-like Receptor 4 Deficiency Facilitates α-Synuclein Propagation and Neurodegeneration in a Mouse Model of Prodromal Parkinson’s Disease.” Parkinsonism & Related Disorders, vol. 91, Elsevier, 2021, pp. 59–65, doi:10.1016/j.parkreldis.2021.09.007. short: S. Venezia, W. Kaufmann, G.K. Wenning, N. Stefanova, Parkinsonism & Related Disorders 91 (2021) 59–65. date_created: 2022-01-09T23:01:26Z date_published: 2021-10-01T00:00:00Z date_updated: 2023-08-17T06:36:01Z day: '01' ddc: - '610' department: - _id: EM-Fac doi: 10.1016/j.parkreldis.2021.09.007 external_id: isi: - '000701142900012' pmid: - '34530328' file: - access_level: open_access checksum: 360681585acb51e80d17c6b213c56b55 content_type: application/pdf creator: alisjak date_created: 2022-01-10T13:41:40Z date_updated: 2022-01-10T13:41:40Z file_id: '10612' file_name: 2021_Parkinsonism_Venezia.pdf file_size: 6848513 relation: main_file success: 1 file_date_updated: 2022-01-10T13:41:40Z has_accepted_license: '1' intvolume: ' 91' isi: 1 language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 59-65 pmid: 1 publication: Parkinsonism & Related Disorders publication_identifier: eissn: - 1873-5126 issn: - 1353-8020 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 91 year: '2021' ...