Preface to the Special Issue “Matrix Metalloproteinases in Health and Disease”

This preface introduces a collection of new work focused on matrix metalloproteinases (MMPs) and select MMP substrates in the nervous system. Discovered over 60 years ago during the study of collagen degradation during tadpole tail metamorphosis by Gross and Lapiere, MMPs are now known to play critical roles in adaptive and non-adaptive physiological processes in varied species. Though early studies focused predominantly on their role in inflammation, wound healing, and angiogenesis, work during the last 20 years has expanded to include an abundance of studies related to MMPs and their substrates in brain disease and plasticity. Particularly novel and intriguing studies are numerous and include those related to the role of MMPs in mood and memory, as well as studies of select MMP substrates in critical period closure. The manuscripts herein include a review of MMP-9, an MMP that is released from resident cells of the brain, including neurons and microglia, as well as a comprehensive review of perineuronal nets (PNNs), which are composed of MMP substrates including brevican. Additional manuscripts focus on fragile X messenger ribonucleoprotein 1 product (FMRP) in the translational regulation of aggrecan, an important PNN component, as well as manuscripts showing PNN chondroitin sulfate-glycosaminoglycan compositional changes in a mouse model of tauopathy, a novel localization of PNN-like structures in the enteric nervous system, a mechanism by which MMP-2 could contribute to the disruption of the blood-brain barrier, and differential effects of a sirtuin agonist on glial and neuronal MMP release.