Sugar in Neurons May Protect Against Alzheimer's

Scientists at the Buck Institute for Research on Aging have made a new discovery about neuron metabolism, and in particular about how sugar is stored and processed: according to a study published in the journal Nature Metabolism , researchers have shown that the way in which sugar molecules are “broken down” in neurons could protect the brain from the accumulation of toxic proteins – one of the main suspects in the development of Alzheimer’s disease – and from cognitive degeneration.

A question of glycogen

The molecule under examination is glycogen, a sugar that essentially acts as an energy reserve stored in the liver, muscles, and, in smaller quantities, in the brain, in particular in “support cells,” called astrocytes.

Until now, however, the role of these glycogen pockets in neurons was thought to be almost negligible; but the study just published disproves, at least partially, this perspective: "Our work", said Pankaj Kapahi , first author of the article, "contradicts the hypothesis according to which glycogen in the brain is almost useless, and the implications of this discovery could be significant. Glycogen stored in the brain could play an important role in the pathogenesis of various disorders".

The team of experts who conducted the study examined models of tauopathies (the group of neurodegenerative diseases linked to the accumulation of the protein tau in the brain, including Alzheimer's) in both humans and fruit flies, always noting an abnormal accumulation of glycogen. It also appears, the researchers say, that this accumulation contributes to the progression of the disease, since tau is able to chemically bind to glycogen, trapping it and preventing its degradation.

Breaking sugars to feel better

A little more detail on this previously overlooked metabolic aspect. When glycogen cannot be degraded, neurons lose the ability to better manage oxidative stress, a phenomenon crucially linked to aging and neurodegenerative diseases. The reverse is also true, and here is the most interesting part of the discovery: the researchers realized that restoring the activity of an enzyme called glycogen phosphorylase (GlyP), responsible for the degradation of glycogen, reduced the damage related to the accumulation of tau protein in neurons of fruit flies and in those derived from human stem cells. "In this way," commented Sudipta Bar , another co-author of the study, "brain cells were able to 'detoxify' themselves more effectively, reduce the damage suffered and even extend their lifespan."

Food restriction works

It doesn't end there. In their study, the researchers also showed that calorie and food restriction improve glycogen metabolism and consequently mitigate problems related to the accumulation of tau protein. And it seems that a similar result can be obtained by administering drugs that "mimic" food restriction, such as new anti-obesity molecules: "Our work," concluded Kapahi, "explains why GLP-1-based drugs, now widely used for weight loss, are also promising against dementia: the reason is probably because they mimic the effects of food restriction. By discovering how neurons 'manage' sugars, we may have discovered a new therapeutic avenue, which targets the internal chemistry of neurons to counteract age-related decline and neurodegeneration."