PT  - JOURNAL ARTICLE
AU  - Miranda, HV
AU  - Gomes, MA
AU  - Branco dos Santos, J
AU  - Giorgini, F
AU  - Outeiro, TF
TI  - B08 Glycation Modulates Huntingtin Aggregation And Toxicity
AID  - 10.1136/jnnp-2014-309032.36
DP  - 2014 Sep 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - A11--A11
VI  - 85
IP  - Suppl 1
4099  - http://jnnp.bmj.com/content/85/Suppl_1/A11.3.short
4100  - http://jnnp.bmj.com/content/85/Suppl_1/A11.3.full
SO  - J Neurol Neurosurg Psychiatry2014 Sep 01; 85
AB  - Glycation, an age-dependent posttranslational protein modification, has been reported in several neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. This non-enzymatic reaction between reducing sugars and free amino-groups from proteins, interferes with the aggregation process of proteins such as amyloid-beta and alpha-synuclein. As methylglyoxal (MGO) is the most important glycation agent, here we interrogated whether MGO glycation could also play a role in huntingtin (HTT) biology. Using a versatile yeast model, we observed that glycation increased the aggregation of a HTT exon 1 fragment (HTT72Q or HTT103Q). We also observed that glycation promoted aggregation and toxicity in human neuroglioma cells expressing HTT103Q. Notably, MGO treatment of HTT93Q transgenic flies potentiates neuronal loss in a dose-dependent manner. In total, this study suggests that glycation might contribute to huntingtin dysfunction and may constitute a novel target for therapeutic intervention in HD.