Extracellular Matrix Recycling as a Novel Plasticity Mechanism With a Potential Role in Disease

The extracellular matrix (ECM) stabilizes neural circuits and synapses in the healthy brain, while also retaining the ability to be remodeled, to allow synapses to be plastic. A well-described mechanism for ECM remodeling is through the regulated secretion of proteolytic enzymes at the synapse, together with the synthesis of new ECM molecules. The importance of this process is evidenced by the large number of brain disorders that are associated with a dysregulation of ECM-cleaving protease activity. While most of the brain ECM molecules are indeed stable for remarkable time periods, evidence in other cell types, as cancer cells, suggests that at least a proportion of the ECM molecules may be endocytosed regularly, and could even be recycled back to the ECM. In this review, we discuss the involvement of such a mechanism in the brain, under physiological activity conditions and in relation to synapse and brain disease.

Automated summary

The extracellular matrix (ECM) plays a crucial role in stabilizing neural circuits and synapses in the healthy brain, while also being able to undergo remodeling. This process involves regulated secretion of proteolytic enzymes and synthesis of new ECM molecules. Dysregulation of ECM-cleaving protease activity is associated with various brain disorders. Furthermore, evidence suggests that some ECM molecules may undergo endocytosis and be recycled in other cell types, including cancer cells.