Profilin 1 Controls A Microglial Cytoskeleton Checkpoint To Prevent Senescence And Premature Synaptic Decline
Our brains rely on specialized immune cells, called microglia, to stay healthy and function properly. These cells are constantly monitoring the brain environment, clearing debris, and supporting the connections between neurons, known as synapses. However, as we age, microglia can become senescent, meaning they stop functioning correctly and instead release harmful substances that can damage synapses and impair brain function.
Recent research has uncovered a key player in preventing this detrimental process: a protein called Profilin 1. This protein is vital for maintaining the internal scaffolding, or cytoskeleton, of microglia. Think of the cytoskeleton as the cell’s skeleton, allowing it to move, change shape, and respond to its surroundings. When Profilin 1 is lost, this internal scaffolding collapses, rendering the microglia unable to perform their protective duties, such as responding to injuries in the brain.
This disruption triggers a cascade of events, leading to the microglia entering a state of premature aging and releasing inflammatory molecules. These harmful substances then negatively impact the surrounding synapses, leading to problems with energy production in brain cells and affecting how neurons communicate. Ultimately, these cellular changes can manifest as alterations in behavior, including changes in anxiety and how risks are assessed.
Given that levels of this protein naturally decrease in microglia as humans age, these findings suggest that targeting the Profilin 1-cytoskeleton pathway could be a promising strategy to bolster brain resilience and protect against age-related cognitive decline.
Source: link to paper