Gene Expression Profiling of Mitochondrial Oxidative Phosphorylation OXPHOS Complex I in Friedreich Ataxia FRDA PatientsReportar como inadecuado




Gene Expression Profiling of Mitochondrial Oxidative Phosphorylation OXPHOS Complex I in Friedreich Ataxia FRDA Patients - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Friedreich ataxia FRDA is the most frequent progressive autosomal recessive disorder associated with unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene, which encodes for the mitochondrial frataxin protein. The number of repeats correlates with disease severity, where impaired transcription of the FXN gene results in reduced expression of the frataxin protein. Gene expression studies provide insights into disease pathogenicity and identify potential biomarkers, an important goal of translational research in neurodegenerative diseases. Here, using real-time PCR RT-PCR, the expression profiles of mitochondrial mtDNA and nuclear DNA nDNA genes that encode for the mitochondrial subunits of respiratory oxidative phosphorylation OXPHOS complex I in the blood panels of 21 FRDA patients and 24 healthy controls were investigated. Here, the expression pattern of mtDNA-encoded complex I subunits was distinctly different from the expression pattern of nDNA-encoded complex I subunits, where significant p<0.05 down-regulation of the mitochondrial ND2, ND4L, and ND6 complex I genes, compared to controls, were observed. In addition, the expression pattern of one nDNA-encoded gene, NDUFA1, was significantly p<0.05 down-regulated compared to control. These findings suggest, for the first time, that the regulation of complex I subunit expression in FRDA is complex, rather than merely being a reflection of global co-regulation, and may provide important clues toward novel therapeutic strategies for FRDA and mitochondrial complex I deficiency.



Autor: Mohammad Hossein Salehi, Behnam Kamalidehghan, Massoud Houshmand , Goh Yong Meng, Majid Sadeghizadeh, Omid Aryani, Shahriar Nafis

Fuente: http://plos.srce.hr/



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