Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer's disease mouse model.
Alzheimers Res Ther
; 16(1): 101, 2024 05 06.
Article
em En
| MEDLINE
| ID: mdl-38711159
ABSTRACT
BACKGROUND:
In Alzheimer's disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue.METHODS:
Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113).RESULTS:
Treatment resulted in significant reductions in amyloid-beta (Aß) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice.CONCLUSIONS:
This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camundongos Transgênicos
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Microglia
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Placa Amiloide
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Modelos Animais de Doenças
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Dendrímeros
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article