The excessive accumulation of glycogen in the brain worsens oxidative stress and damage on neurons, increasing dementia risk. But an enzyme (and diet) can help.
The search for new therapies against dementias could boast of a new, unexpected ally: The metabolism of sugars in the brain. Improving the demolition of glycogen (a reserve sugar) in the neurons in fact seems to mitigate the damage inflicted on brain cells from the Tau protein, closely linked to the cognitive decline in Alzheimer’s disease. The discovery was published on Nature Metabolism.
Tau and excess of glycogen: a vicious circle for dementias
The excess glucose that we take through carbohydrates accumulates in the muscles and in the liver where it forms a “escort”, the glycogen. Small quantities of glycogen are also present in the brain, especially in support of astrocytes, the star -shaped cells that dialogue with the neurons. The role of glycogen in neurons was so far considered completely negligible.
Based on the new study, led by scientists of the Buck Institute for Research on aging, California, too glycogen in neurons could contribute to pathologies. Scientists found that, in cellular models of neurodegenerative diseases linked to an anomalous metabolism of the Tau protein (such as Alzheimer’s), Neurons accumulate glycogen in excessive quantitiesand this phenomenon can aggravate the disease.
Tau sticking to glycogen and prevents its demolition: all this weighs down oxidative stressa biological process that accelerates the aging of the brain.
Demolish to cure
Restoring the activity of an enzyme – the phosphorilasiswho intervenes in the demolition of glycogen – was possible Reduce the damage from Tau accumulation In all cellular models studied (both in neurons deriving from human stem and in the neurons of fruit midges). The neurons supported by the enzyme have in fact used glycogeninstead of keeping it only as a reserve, and have transformed it into molecules that fight oxidative stress in the brain.
Scientists have also discovered that calorie restriction, several times in the past associated with anti -aging properties and greater life – has naturally increased the activity of the phosphorylase and improved the survival of neurons in the models of Tau pathology studied.
This is interesting both because the benefits of caloric restriction on glycogen demolition can be reproduced pharmacologically, both because it could explain The association between the use of antidiabetic and anti-obesity drugs and protection from dementia.
For some time, in fact, the agonist drugs of the GLP-1 receptor such as the Ozempic have been connected, in observational studies, to a reduction in the risk of dementia, even if the mechanism below has not yet been clarified. A possible reason could be the ability of these medicines to mimic the effects of a caloric restriction and of act on glycogen reserves in the brain.
Cell chemistry against dementia
Finally, scientists confirmed the existence of glycogen accumulations in neurons derived from patients with front-time dementia, a group of non-alzheimer neurodegenerative disorders, and proven that strengthening the action of phosphorilasis has on these neurons a protective effect. The discovery could serve in future therapies against cognitive decline.
