Heterochromatic genome instability and neurodegeneration sharing similarities with Alzheimer's disease in old Bmi1+/- mice.
Sci Rep
; 9(1): 594, 2019 01 24.
Article
em En
| MEDLINE
| ID: mdl-30679733
ABSTRACT
Sporadic Alzheimer's disease (AD) is the most common cause of dementia. However, representative experimental models of AD have remained difficult to produce because of the disease's uncertain origin. The Polycomb group protein BMI1 regulates chromatin compaction and gene silencing. BMI1 expression is abundant in adult brain neurons but down-regulated in AD brains. We show here that mice lacking one allele of Bmi1 (Bmi1+/-) develop normally but present with age cognitive deficits and neurodegeneration sharing similarities with AD. Bmi1+/- mice also transgenic for the amyloid beta precursor protein died prematurely and present aggravated disease. Loss of heterochromatin and DNA damage response (DDR) at repetitive DNA sequences were predominant in Bmi1+/- mouse neurons and inhibition of the DDR mitigated the amyloid and Tau phenotype. Heterochromatin anomalies and DDR at repetitive DNA sequences were also found in AD brains. Aging Bmi1+/- mice may thus represent an interesting model to identify and study novel pathogenic mechanisms related to AD.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Heterocromatina
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Proteínas Proto-Oncogênicas
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Instabilidade Genômica
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Doença de Alzheimer
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Complexo Repressor Polycomb 1
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2019
Tipo de documento:
Article