Assuntos
Doenças Assintomáticas , Neoplasias Encefálicas/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Hemangioma Cavernoso do Sistema Nervoso Central/sangue , Interleucinas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias Encefálicas/diagnóstico por imagem , Estudos de Coortes , Feminino , Seguimentos , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, is caused by a CAG repeat expansion in the ATXN7 gene coding region. Disease onset and progression are highly variable between patients, thus identification of specific/sensitive biomarkers that can improve the monitoring of disease progression is an immediate need. Because altered expression of circulating microRNAs (miRNAs) has been shown in various neurological diseases, they could be useful biomarkers for SCA7. In this study, we showed, to our knowledge for the first time, the expression profile of circulating miRNAs in SCA7. Using the TaqMan profiling low density array (TLDA), we found 71 differentially expressed miRNAs in the plasma of SCA7 patients, compared with healthy controls. The reliability of TLDA data was validated independently by quantitative real-time polymerase chain reaction in an independent cohort of patients and controls. We identified four validated miRNAs that possesses the diagnostic value to discriminate between healthy controls and patients (hsa-let-7a-5p, hsa-let7e-5p, hsa-miR-18a-5p, and hsa-miR-30b-5p). The target genes of these four miRNAs were significantly enriched in cellular processes that are relevant to central nervous system function, including Fas-mediated cell-death, heparansulfate biosynthesis, and soluble-N-ethylmaleimide-sensitive factor activating protein receptor pathways. Finally, we identify a signature of four miRNAs associated with disease severity that discriminate between early onset and adult onset, highlighting their potential utility to surveillance disease progression. In summary, circulating miRNAs might provide accessible biomarkers for disease stage and progression and help to identify novel cellular processes involved in SCA7.
Assuntos
MicroRNA Circulante/genética , Perfilação da Expressão Gênica , Ataxias Espinocerebelares/genética , Adulto , MicroRNA Circulante/sangue , MicroRNA Circulante/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/sangue , Ataxias Espinocerebelares/diagnósticoRESUMO
Psychiatric disorders are complex diseases involving exogenous and endogenous factors. Biomarkers for diagnosis or prediction of successful treatment are not existent. In addition, the molecular basis of these diseases is still poorly understood. Blood plasma represents the most complex proteome as it contains subproteomes from several body tissues. However, the high abundance of some little proteins can obscure the analysis of hundreds of low abundance proteins, which are potential biomarkers. Therefore, removal of these high abundance proteins is pivotal in any proteomic study of plasma. Here, we present a method of depleting these proteins using immunoaffinity liquid chromatography.