biostudies-literatureVicente Miranda HMedical Research Council36798https://www.ebi.ac.uk/biostudies/studies/S-EPMC5114697biostudies-literatureUnknown6Protein glycation is an age-dependent posttranslational modification associated with several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. By modifying amino-groups, glycation interferes with folding of proteins, increasing their aggregation potential. Here, we studied the effect of pharmacological and genetic manipulation of glycation on huntingtin (HTT), the causative protein in Huntington's disease (HD). We observed that glycation increased the aggregation of mutant HTT exon 1 fragments associated with HD (HTT72Q and HTT103Q) in yeast and mammalian cell models. We found that glycation impairs HTT clearance thereby promoting its intracellular accumulation and aggregation. Interestingly, under these conditions autophagy increased and the levels of mutant HTTScientific reportsGlycation potentiates neurodegeneration in models of Huntington's disease.PMC5114697MR/N00373X/1Lopes LVLazaro DFBreda CHerrera FOuteiro TFGomes MABranco-Santos JVicente Miranda HGiorgini FfalseGlycation potentiates neurodegeneration in models of Huntington's disease.Protein glycation is an age-dependent posttranslational modification associated with several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. By modifying amino-groups, glycation interferes with folding of proteins, increasing their aggregation potential. Here, we studied the effect of pharmacological and genetic manipulation of glycation on huntingtin (HTT), the causative protein in Huntington's disease (HD). We observed that glycation increased the aggregation of mutant HTT exon 1 fragments associated with HD (HTT72Q and HTT103Q) in yeast and mammalian cell models. We found that glycation impairs HTT clearance thereby promoting its intracellular accumulation and aggregation. Interestingly, under these conditions autophagy increased and the levels of mutant HTT2016-01-01T00:00:00Z2016 Nov2025-04-25T19:18:44.417Z2019-03-27T02:29:18ZS-EPMC51146972785717610.1038/srep36798