Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics.
Int J Nanomedicine
; 10 Spec Iss: 281-92, 2015.
Article
em En
| MEDLINE
| ID: mdl-27601894
ABSTRACT
Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Encéfalo
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Soroalbumina Bovina
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Produtos Finais de Glicação Avançada
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Apoptose
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Microglia
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Neurônios Dopaminérgicos
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Nanomedicina Teranóstica
Tipo de estudo:
Observational_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Nanomedicine
Ano de publicação:
2015
Tipo de documento:
Article