Metalloproteinases and neurodegenerative diseases: pathophysiological and therapeutic perspectives

Abstract

Matrix metalloproteinases (MMPs) are important in the central nervous system from growth and development to brain injury and repair. Cerebral blood vessels are central to the role of the MMPs in the brain. MMPs are a final common pathway for disruption of the blood–brain barrier through proteolysis of the extracellular matrix proteins in the basal lamina surrounding cerebral capillaries and in the unraveling of the essential structure formed by tight-junction pro-teins that maintain the protected microenvironment necessary for neuronal function. MMPs are major factors in the pathological processes that occur in the brain with hypoxia/ischemic injury, multiple sclerosis, infection, and vascular causes of dementia. In each of these neurological disorders, the MMPs disrupt the blood–brain barrier and damage the myelinated nerve fibers. Inhibitors of MMPs block injury in each of these illnesses in animal models. It is important to develop MMP inhibitors that can be translated from animal studies to human treatments.