Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes.
Acta Neuropathol
; 131(3): 379-91, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-26576561
ABSTRACT
Extracellular alpha-synuclein (αsyn) oligomers, associated to exosomes or free, play an important role in the pathogenesis of Parkinson's disease (PD). Increasing evidence suggests that these extracellular moieties activate microglia leading to enhanced neuronal damage. Despite extensive efforts on studying neuroinflammation in PD, little is known about the impact of age on microglial activation and phagocytosis, especially of extracellular αsyn oligomers. Here, we show that microglia isolated from adult mice, in contrast to microglia from young mice, display phagocytosis deficits of free and exosome-associated αsyn oligomers combined with enhanced TNFα secretion. In addition, we describe a dysregulation of monocyte subpopulations with age in mice and humans. Accordingly, human monocytes from elderly donors also show reduced phagocytic activity of extracellular αsyn. These findings suggest that these age-related alterations may contribute to an increased susceptibility to pathogens or abnormally folded proteins with age in neurodegenerative diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Monocitos
/
Microglía
/
Alfa-Sinucleína
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Acta Neuropathol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania