The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration
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 disord...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/178457 |
| Acceso en línea: | https://hdl.handle.net/11441/178457 https://doi.org/10.1093/braincomms/fcaf087 |
| Access Level: | acceso abierto |
| Palabra clave: | Microglia Prion-like Alpha-synuclein Amyloid-beta Tau |
| Sumario: | 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. |
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