---
_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'
...