Boosting glucose metabolism in glial cells reduces neurodegeneration in fruit flies

Researchers at Tokyo Metropolitan University have discovered that a reduced glucose metabolism in glial cells, a type of cell in our nervous system, a key role plays in degeneration caused by Alzheimer’s disease. With the help of fruit fly rhetinas, they showed that promoting glucose metabolism in glial cells with tau protein structure, such as in Alzheimer’s patients, helps to relieve the inflammation and degeneration of photoreceptor. Their findings are an exciting new therapeutic target for the treatment of neurodegenerative disorders.

Alzheimer’s disease (AD) is the world’s main cause of dementia in the elderly and remains a devastating impact on the quality of people’s life. Scientists work against the clock to unravel the enormous network of mechanisms, causing Ad to influence our nervous system. For example, we know that AD is characterized by a structure of Tau protein in cells, but the ways in which this leads to neurodegeneration is not yet fully understood.

A team led by Professor Kanae Ando of the Tokyo Metropolitan University has drawn their attention to how the structure of tau protein glial cells, non-neuronal cells in our central nervous system influences that help support, nourish and protect neurons. It is important that the ways in which glial cells work have a lot to do with what happens in AD patients. For example, glial cells are known that they are cleaning away the abnormal structure of proteins, accompanied by an inflammatory response; Neuro -inflammation is a core pathology of AD. They play an important role in helping neurons to stay fed by metabolizing glucose; A drastic decrease in brain glucose metabolism is another characteristic of AD patients. However, the relationship between changes in glial cellglucose metabolism and Tau protein structure was unknown.

With the help of Drosophila fruit flies as a model, the team first showed that flies adapted to have a Tau protein structure in the retina, showed neurodegeneration, swelling in nearby areas and the formation of abnormal inclusions. They were able to prove that the last of these was caused by the fact that Glia cells were abnormally active. To investigate how this connection was related to glucose metabolism, they could use genetic modification techniques to express more of a glucose transport protein (GLUT) in gla cells. Amazingly, this led to oppression of neurodegeneration and fewer inflammations, although it did not lead to changes in tau protein structure. This shows that the structure of Tau protein causes glial cells to suffer from a significant fall in glucose metabolism.

The team proposes that glucose metabolism can be a new target for new therapies for neurodegenerative disorders. Diseases such as Parkinson’s, for example, are also characterized by neuro inflammation. Any progress that can cure, prevent or even delay the start of one of these conditions promise to have a game-changing impact on human society.

This work was supported by a JSPS subsidy for JSPS Research Fellows 18J21936, The Takeda Science Foundation, a research price of the Japan Foundation for Aging and Health, NIG-Joint [25A2019]A subsidy for scientific research into challenging research (Exploratory) [JSPS KAKENHI Grant number 19K21593]A subsidy for scientific research (B) [24K02860]A research subsidy from the National Institute of Aging/National Institutes of Health [RF1AG071557]And the TMU Strategic Research Fund.