A team of researchers from CEDOC – FCM UNL (Center for the Study of Chronic Diseases, Faculty of Medical Sciences, Universidade Nova de Lisboa) carried out a study that indicates that high levels of sugar in the body accelerate the effects of neurodegenerative diseases, such as Huntington's disease.

Previous studies indicated that hyperglycemia, present in diabetic patients, accelerates the degradation of nerve cells in the brain, through the action of protein glycation. Glycation is a negative and toxic reaction that glucose, at high levels, promotes in the body. It happens when carbohydrates bind to proteins, causing changes that affect the correct functioning of cells. Therefore, diabetics are more predisposed to developing neurodegenerative diseases and, consequently, present irreversible organic lesions.

Using Huntington's Disease as a model, a rare neurodegenerative disease that affects patients' cognitive and motor skills, researchers Tiago Outeiro and Hugo Miranda decided to study the effects of huntingtin protein glycation in the brain. By manipulating the levels of metabolized sugar in human cells and yeast, scientists triggered protein glycation and observed an increase in the accumulation of the protein huntingtin , which led to its aggregation and accelerated the destruction of nerve cells.

The researchers also performed in vivo studies on fruit flies. In this case, genetic manipulation made it possible to relate the effects of glycation to the neurogeneration of flies and the reduction of their lifespan.

The researchers therefore concluded that “very common factors in the population such as hyperglycemia, prevalent in pre-diabetics and diabetics, thus have a direct effect on specific diseases, such as Huntington's disease, causing it to manifest early ”, as stated in the NOVA Medical School Press Release .

As Huntington's disease is associated with protein aggregation, the results of this research pave the way for studying glycation as a new target for this pathology.

The study developed was financed by FCT through Studentships individual doctoral and post-doctoral programs and the FCT Researcher program. 

Principal Investigator: Tiago Outeiro from Cell and Molecular Neuroscience Lab
Original article (Nature) “ Glycation potentiates neurodegeneration in models of Huntington's disease “