Bengt Winblad, MD, PhD, Karolinska Institutet, Solna, Sweden, explores the potential of proteolysis targeting chimera (PROTAC) molecules in targeting Alzheimer’s disease (AD) pathology. Inspired by the treatment mechanisms observed in metastatic cancers, PROTACs work by binding to abnormal proteins like tau, inducing selective intracellular proteolysis to degrade protein targets via the ubiquitin–proteasome system, and then cycling back for more. As well as being cheap and easy to produce, the circular mechanism could allow for lower concentrations and reduced side effects compared to traditional drugs. This approach targets the production of amyloid beta and tau, particularly within neurons, making it complementary to current antibody treatments for Alzheimer’s. While the effect size seen in studies to date has not been optimal, combining small-molecule PROTACs with existing therapies is promising. This interview took place at the AD/PD™ 2024 congress in Lisbon, Portugal.
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