Protective properties of lysozyme on ß-amyloid pathology: implications for Alzheimer disease.
Neurobiol Dis
; 83: 122-33, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26334479
ABSTRACT
The hallmarks of Alzheimer disease are amyloid-ß plaques and neurofibrillary tangles accompanied by signs of neuroinflammation. Lysozyme is a major player in the innate immune system and has recently been shown to prevent the aggregation of amyloid-ß1-40 in vitro. In this study we found that patients with Alzheimer disease have increased lysozyme levels in the cerebrospinal fluid and lysozyme co-localized with amyloid-ß in plaques. In Drosophila neuronal co-expression of lysozyme and amyloid-ß1-42 reduced the formation of soluble and insoluble amyloid-ß species, prolonged survival and improved the activity of amyloid-ß1-42 transgenic flies. This suggests that lysozyme levels rise in Alzheimer disease as a compensatory response to amyloid-ß increases and aggregation. In support of this, in vitro aggregation assays revealed that lysozyme associates with amyloid-ß1-42 and alters its aggregation pathway to counteract the formation of toxic amyloid-ß species. Overall, these studies establish a protective role for lysozyme against amyloid-ß associated toxicities and identify increased lysozyme in patients with Alzheimer disease. Therefore, lysozyme has potential as a new biomarker as well as a therapeutic target for Alzheimer disease.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Encéfalo
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Muramidase
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Peptídeos beta-Amiloides
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Doença de Alzheimer
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article