Researchers from the University of Pennsylvania report that 4-phenylbutyrate may slow Alzheimer’s progression in mice
Researchers at the Perelman School of Medicine, University of Pennsylvania, have identified a compound called 4-phenylbutyrate (PBA) that can clear toxic protein buildup in the brain associated with Alzheimer’s disease. In mouse studies, PBA appeared to slow or reduce disease progression, a finding published in Biology of Aging and noted as a potential step toward therapies for cognitive decline.
4-phenylbutyrate is a fatty acid molecule that helps prevent the accumulation of harmful proteins in the brain, including amyloid plaques and tau tangles linked to Alzheimer’s disease. By restoring proteostasis, it supports the balance of cellular proteins, which is crucial for maintaining normal brain function.
In laboratory experiments, mice were given PBA via intraperitoneal injection. This administration reduced proteotoxic stress caused by misfolded proteins. Young mice with spatial navigation challenges treated with PBA demonstrated improved ability to differentiate moving from stationary objects in a cognitive test. Middle-aged mice also showed a reduction in memory deficits after therapy, suggesting benefits across different life stages.
Further observations indicated a decline in amyloid plaque numbers and a slowdown in the processes that form these plaques as treatment continued. An important practical point is that drugs based on PBA can cross the blood-brain barrier through the bloodstream, enabling direct brain action.
There are related studies in related facilities exploring post-stroke rehabilitation improvements, underscoring the broader interest in metabolic and proteostatic approaches to brain health in diverse models and conditions.