In a new study, researchers have found a potential drug that may prevent neuronal death through glucose metabolism modification in stressed neurons.
The new drug could have applications in neurological diseases including Alzheimer’s, Huntington’s diseases, traumatic brain injury and ischemic stroke.
The research was conducted by an international team of scientists from Gero Discovery LLC, the Institute of Biomedical Research of Salamanca, and Nanosyn, Inc.
Brain injuries and neurological disorders are key causes of death worldwide.
According to WHO, stroke is the second-most common cause of mortality, and more than a third of people who survived a stroke have a severe disability.
And as the population ages, millions more people are poised to develop Alzheimer’s or Parkinson’s diseases in the near future.
However, there are no effective treatments for major neurodegenerative diseases.
It is thus critically important to understand the biology of these diseases and to identify new drugs capable of improving quality of life, survival, and, in the best-case scenario, curing the disease completely.
Glycolysis is generally considered as the metabolic pathway essential for cell survival since it meets cell energy needs in conditions of intensive energy consumption.
However, it is known that in brain tissue, the situation is quite different—different cell types show distinct glucose metabolism patterns.
In neurons, only a small portion of glucose is consumed via the glycolysis pathway. Astrocytes provide nutrients to neurons and use glycolysis to metabolize glucose.
These differences are mostly due to a protein called PFKFB3, which is normally absent in neurons and active in astrocytes.
In the case of certain neurological diseases, stroke being one of them, the amount of active PFKFB3 increases in neurons, which is highly stressful for these cells and leads to cell death.
In the study, the team suggested and further confirmed that a small molecule, the inhibitor of PFKFB3, may prevent cell death in the case of ischemia injury.
Inhibition of PFKFB3 improves motor coordination of mice after stroke and reduced brain infarct volume.
Moreover, PFKFB3 inhibitor protects neurons from the amyloid-beta peptide, the main component of the amyloid plaques found in the brains of Alzheimer’s disease patients.
The team now is planning to proceed with preclinical trials and to move into clinical trials soon.
These promising results bring hope to dozens of millions of patients suffering from life-threatening neurological diseases.
The lead author of the study is Peter Fedichev, a scientist and biotech entrepreneur from Gero Discovery.
The study is published in Scientific Reports.
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