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Researchers have delved into developing small molecule inhibitors targeting protein-protein interactions in Alzheimer's disease.


Researchers from the CMD and the TREAT-AD consortium have delved into the development of small molecule inhibitors targeting protein-protein interactions involving moesin (MSN) and CD44. These microglial proteins play a crucial role in Alzheimer’s disease (AD). Proteomic studies have revealed their increased abundance in AD patients, with levels closely linked to cognitive decline and amyloid burden. The MSN FERM domain interacts with the phospholipid PIP2 and CD44’s cytoplasmic tail. By inhibiting the MSN-CD44 interaction, researchers hope to mitigate AD-related neuronal damage. The researchers used structural analyses, mutational studies, and phage-display experiments to understand how CD44 binds to the FERM domain of MSN. High-throughput screening of a large chemical library identified compounds disrupting this interaction, offering promise for future drug development efforts.