---
_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. <i>Parkinsonism &#38; Related Disorders</i>. 2021;91:59-65.
    doi:<a href="https://doi.org/10.1016/j.parkreldis.2021.09.007">10.1016/j.parkreldis.2021.09.007</a>
  apa: Venezia, S., Kaufmann, W., Wenning, G. K., &#38; Stefanova, N. (2021). Toll-like
    receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration
    in a mouse model of prodromal Parkinson’s disease. <i>Parkinsonism &#38; Related
    Disorders</i>. Elsevier. <a href="https://doi.org/10.1016/j.parkreldis.2021.09.007">https://doi.org/10.1016/j.parkreldis.2021.09.007</a>
  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.” <i>Parkinsonism &#38; Related
    Disorders</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.parkreldis.2021.09.007">https://doi.org/10.1016/j.parkreldis.2021.09.007</a>.
  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,” <i>Parkinsonism &#38; Related Disorders</i>,
    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 &#38; 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.”
    <i>Parkinsonism &#38; Related Disorders</i>, vol. 91, Elsevier, 2021, pp. 59–65,
    doi:<a href="https://doi.org/10.1016/j.parkreldis.2021.09.007">10.1016/j.parkreldis.2021.09.007</a>.
  short: S. Venezia, W. Kaufmann, G.K. Wenning, N. Stefanova, Parkinsonism &#38; 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
license: https://creativecommons.org/licenses/by/4.0/
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'
...