Expression of the glucosyltransferases HUGT1 and HUGT2 in Alzheimer?s Disease and Frontotemporal Dementia

MARISOL DELEA; CASTRO OLGA A; SURACE EZEQUIEL

CABA

Simposio; GlycoAr2014; 2014

Fundacion Instituto Leloir

Expression of the glucosyltransferases HUGT1 and HUGT2 in Alzheimer?s Disease and Frontotemporal Dementia Marisol Delea, Alejandra Olga Castro, Miguel Riudavets, Ezequiel Surace Presenting autor: marisoldelea@gmail.com 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 two AD, four FTD and 2 non-demented control brains. HUGT1 and HUGT2 expression was analyzed by Real Time PCR. We observed a statistically significant reduction in HUGT2 expression in 6 of 7 AD-FTD brains compared to controls. Also, HUGT1 expression was slightly reduced in AD-FTD brains. 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.