Next Article in Journal
Cytotoxicity of Different Concentrations of Three Root Canal Sealers on Human Mesenchymal Stem Cells
Previous Article in Journal
Potential Impact of Oral Inflammations on Cardiac Functions and Atrial Fibrillation
Article Menu
Issue 3 (September) cover image

Export Article

Open AccessArticle
Biomolecules 2018, 8(3), 67; https://doi.org/10.3390/biom8030067

Model Senescent Microglia Induce Disease Related Changes in α-Synuclein Expression and Activity

Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
*
Author to whom correspondence should be addressed.
Received: 4 July 2018 / Revised: 24 July 2018 / Accepted: 26 July 2018 / Published: 1 August 2018
(This article belongs to the Special Issue Alpha-Synuclein: From function to Disfunction)
Full-Text   |   PDF [3374 KB, uploaded 1 August 2018]   |  

Abstract

Aging is the most prominent risk factor for most neurodegenerative diseases. However, incorporating aging-related changes into models of neurodegeneration rarely occurs. One of the significant changes that occurs in the brain as we age is the shift in phenotype of the resident microglia population to one less able to respond to deleterious changes in the brain. These microglia are termed dystrophic microglia. In order to better model neurodegenerative diseases, we have developed a method to convert microglia into a senescent phenotype in vitro. Mouse microglia grown in high iron concentrations showed many characteristics of dystrophic microglia including, increased iron storage, increased expression of proteins, such as ferritin and the potassium channel, Kv1.3, increased reactive oxygen species production and cytokine release. We have applied this new model to the study of α-synuclein, a protein that is closely associated with a number of neurodegenerative diseases. We have shown that conditioned medium from our model dystrophic microglia increases α-synuclein transcription and expression via tumor necrosis factor alpha (TNFα) and mediated through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The conditioned medium also decreases the formation of α-synuclein tetramers, associated ferrireductase activity, and increases aggregates of α-synuclein. The results suggest that we have developed an interesting new model of aged microglia and that factors, including TNFα released from dystrophic microglia could have a significant influence on the pathogenesis of α-synuclein related diseases. View Full-Text
Keywords: synuclein; tumor necrosis factor alpha; microglia; aging; iron; cytokines; tetramer synuclein; tumor necrosis factor alpha; microglia; aging; iron; cytokines; tetramer
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Angelova, D.M.; Brown, D.R. Model Senescent Microglia Induce Disease Related Changes in α-Synuclein Expression and Activity. Biomolecules 2018, 8, 67.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top