Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration

Öztürk, Muhammet M. LU ; Emgård, Jakob LU ; García-Revilla, Juan LU orcid ; Fernández-Calle, Rosalía LU ; Yang, Yiyi LU orcid ; Deierborg, Tomas LU orcid and Roos, Tomas T. LU (2025) In Brain Communications 7(2).
Abstract

Numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, the brain's innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like... (More)

Numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, the brain's innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighbouring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha-synuclein, amyloid-beta, Microglia, prion-like, tau
in
Brain Communications
volume
7
issue
2
article number
fcaf087
publisher
Oxford University Press
external identifiers
  • scopus:86000347538
  • pmid:40046336
ISSN
2632-1297
DOI
10.1093/braincomms/fcaf087
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.
id
ab234bac-fc5c-4212-abb9-2b4bd1471a91
date added to LUP
2025-06-25 09:38:45
date last changed
2025-07-09 11:50:40
@article{ab234bac-fc5c-4212-abb9-2b4bd1471a91,
  abstract     = {{<p>Numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, the brain's innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighbouring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.</p>}},
  author       = {{Öztürk, Muhammet M. and Emgård, Jakob and García-Revilla, Juan and Fernández-Calle, Rosalía and Yang, Yiyi and Deierborg, Tomas and Roos, Tomas T.}},
  issn         = {{2632-1297}},
  keywords     = {{alpha-synuclein; amyloid-beta; Microglia; prion-like; tau}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain Communications}},
  title        = {{The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration}},
  url          = {{http://dx.doi.org/10.1093/braincomms/fcaf087}},
  doi          = {{10.1093/braincomms/fcaf087}},
  volume       = {{7}},
  year         = {{2025}},
}