Expresión de las glucosiltransferasas HUGT1 y HUGT2 en Enfermedad de Alzheimer y Demencia Frontotemporal

MARISOL DELEA; OLGA ALEJANDRA CASTRO; MIGUEL RIUDAVETS; EZEQUIEL I. SURACE

Buenos Aires

Simposio; Primer Simposio Argentino de Glicobiología; 2014

Protein folding is a complex and tightly regulated mechanism which ensures that proteins achieve a functional spatial structure. In this regard, glucosyltransferases HUGT act as glycoprotein conformational sensors as they only glucosylate molecules that are not in their native state. Two genes have been identified in humans ? HUGT1 and HUGT2- that share high sequence identity with genes that encode glucosyltransferases in other organisms. Alzheimer?s disease (AD) and Frontotemporal dementia (FTD) are members of the so-called neurodegenerative proteinopathies which are characterized by cerebral accumulation of misfolded proteins. In an effort to study the role of HUGT1 and HUGT2 in neurodegenerative proteinopathies, we analyzed mRNA expression of these genes in cases of AD and FTD. Human brain specimens were obtained from FLENI?s Brain Bank according to Institutional Ethics guidelines. We extracted mRNA from brains of two sporadic AD, two familial AD, two FTD and one non-demented control cases. HUGT1 and HUGT2 expression was analyzed by Real Time PCR. We observed a statistically significant reduction in HUGT2 expression in the sporadic AD and FTD groups compared to control. Also, HUGT1 expression was increased in sporadic AD.  Collectively, these results strongly suggest a pathological role of HUGT2 and HUGT1 in two of the most frequent causes of dementia. Further studies will be needed to elucidate the specific role of each HUGT in neurodegenerative diseases