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Neurobiol Dis ; 43(1): 176-83, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21440067

RESUMO

BACE initiates the amyloidogenic processing of the amyloid precursor protein (APP) that results in the production of Aß peptides associated with Alzheimer's disease (AD). Previous studies have indicated that BACE is elevated in the frontal cortex of AD patients. Golgi-localized γ-ear containing ADP ribosylation factor-binding proteins (GGA) control the cellular trafficking of BACE and may alter its levels. To investigate a link between BACE and GGA expression in AD, frontal cortex samples from AD (N = 20) and healthy, age-matched controls (HC, N =17) were analyzed by immunoblotting. After normalization to the neuronal marker ß-tubulin III, the data indicate an average two-fold increase of BACE protein (p = 0.01) and a 64% decrease of GGA3 in the AD group compared to the HC (p = 0.006). GGA1 levels were also decreased in AD, but a statistical significance was not achieved. qRT-PCR analysis of GGA3 mRNA showed no difference between AD and HC. There was a strong correlation between GGA1 and GGA3 in both AD and HC, but no correlation between BACE and GGA levels. Subcellular fractionation of AD cortex with low levels of GGA proteins showed an alteration of BACE distribution and extensive co-localization with APP. These data suggest that altered compartmentalization of BACE in AD promotes the amyloidogenic processing of APP.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Lobo Frontal/fisiologia , Degeneração Neural/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/biossíntese , Proteínas Adaptadoras de Transporte Vesicular/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/genética , Precursor de Proteína beta-Amiloide/genética , Ácido Aspártico Endopeptidases/genética , Regulação para Baixo/genética , Feminino , Lobo Frontal/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Degeneração Neural/genética , Degeneração Neural/patologia , Regulação para Cima/genética , Rede trans-Golgi/fisiologia
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