0
0
In the ongoing quest for effective treatments for Alzheimer’s disease, researchers at the University of Leeds and Lancaster University in the UK have identified a potential new target — PDE4B, an enzyme found inside cells. This discovery offers hope for improved therapies to enhance the quality of life for individuals grappling with Alzheimer’s disease, the leading cause of dementia and disability in old age.
The enzyme PDE4B plays a crucial role in breaking down cyclic AMP, a molecule involved in regulating various cellular processes. Building on previous research from Australia linking the PDE4B gene to Alzheimer’s disease risk, the UK team explored whether reducing PDE4B activity could mitigate Alzheimer’s disease pathology and serve as a viable treatment strategy. To investigate, they introduced a gene for reduced PDE4B activity into a mouse model of Alzheimer’s disease, known for developing amyloid plaques in the brain, a hallmark feature of the disease.
Results from maze tests assessing memory function revealed that Alzheimer’s disease mice exhibited memory deficits, whereas those with genetically reduced PDE4B activity showed preserved memory. Functional brain imaging further unveiled impaired glucose metabolism, a key energy source for the brain, in Alzheimer’s disease mice, mirroring observations in human patients. However, Alzheimer’s disease mice with reduced PDE4B activity displayed healthy levels of glucose metabolism in the brain.
Delving deeper into the mechanisms involved, the researchers examined gene and protein expression levels in the brain. They found heightened inflammation in the brains of Alzheimer’s disease mice, consistent with Alzheimer’s disease patients, but inflammation levels were lower in mice with reduced PDE4B activity. These findings extend to other proteins implicated in Alzheimer’s disease pathology, suggesting that targeting PDE4B activity holds promise for Alzheimer’s disease treatment, pending further validation of drug candidates targeting the enzyme.
Lead researcher Dr. Steven Clapcote from the University of Leeds expressed optimism about the findings, noting the profound protective effects observed on memory and brain function in the Alzheimer’s disease mouse model. Dr. Neil Dawson, a co-author from Lancaster University, emphasized the potential of PDE4B inhibition as a therapeutic strategy, highlighting the significant improvements observed with even a modest reduction in enzyme activity.
The research, published in the journal Neuropsychopharmacology, received support from various organizations, including the Dunhill Medical Trust, BBSRC, Alzheimer’s Research UK, and the Scientific and Technological Research Council of Turkey.
As the search for effective Alzheimer’s treatments continues, the identification of PDE4B as a potential target offers renewed hope for the development of therapies to combat this devastating neurodegenerative disease.
