A new potential target for the treatment of Alzheimerās disease has been identified: PDE4B. Researchers from the University of Leeds and the University of Lancaster, in the United Kingdom, discovered this.
The results of the study, reported on Neuropsychopharmacology, open new avenues for the fight against Alzheimerās disease, which is the main cause of dementia and disability in old age in the world. As the number of people diagnosed with Alzheimerās disease is growing significantly, there is an urgent need for new treatments aimed at improving the quality of life of those affected.
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The role of the PDE4B enzyme
PDE4B is an enzyme that, inside cells, breaks down a molecule, known as cyclic AMP, which regulates a series of cellular processes. Based on an Australian study that identified the PDE4B gene as a risk factor for the development of Alzheimerās disease, the British research team focused its investigation on understanding whether reducing PDE4B activity could protect against Alzheimerās and , consequently, represent a valid therapeutic approach.
To this end, scientists introduced a gene for reducing PDE4B activity into a mouse model of Alzheimerās disease, with amyloid plaques in the brain, a typical pathological feature of the disease. The researchers observed that Alzheimerās mice showed memory deficits in maze tests, but memory was not impaired in Alzheimerās mice with genetically reduced PDE4B activity. Using functional brain imaging, the research team found that the metabolism of glucose, the brainās main source of energy, was impaired in Alzheimerās mice, as in patients with the disease. However, mice with genetically reduced PDE4B activity showed healthy levels of glucose metabolism in the brain.
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The mouse experiment
To understand the mechanisms involved, the researchers then examined gene and protein expression levels in the brain. The scientists identified increased inflammation in the brains of Alzheimerās mice, like that found in patients with the disease, but the inflammation was less in Alzheimerās mice with genetically reduced PDE4B activity.
Similar effects have been observed for a number of other proteins involved in Alzheimerās pathology. Overall, the data suggest that reducing PDE4B activity could be a possible approach for treating Alzheimerās disease, although further research is needed to validate the use of drugs that target the enzyme.
Not just Alzheimerās
āReducing PDE4B enzyme activity had a profound protective effect on memory and glucose metabolism in the Alzheimerās mouse model, despite these mice showing no decrease in the number of amyloid plaques in the brain,ā he said Steven Clapcote, Principal Investigator at the University of Leeds. āThis raises the prospect that reducing PDE4B activity may protect against cognitive impairment not only in Alzheimerās disease, but also in other forms of dementia, such as Huntingtonās disease,ā Clapcote continued.
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āThese findings offer real hope for the development of new treatments that will benefit Alzheimerās disease patients in the future,ā he said Neil Dawson, from Lancaster University and co-author of the work. āIt was interesting to find that reducing PDE4B activity by just 27% can dramatically rescue memory, brain function and inflammation in mice with the disease,ā Dawson continued. āThe next step is to verify whether drugs that inhibit PDE4B have similar beneficial effects in the Alzheimerās mouse model, so as to test their potential efficacy in the disease,ā concluded Dawson.