The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). The major pathological outcomes of the disease are the loss of blood-brain barrier (BBB) integrity and the development of reactive astrogliosis and MS plaque. For the disease to occur, the non-resident cells must enter into the immune-privileged CNS through a breach in the relatively impermeable BBB. It has been demonstrated that matrix metalloproteinases (MMPs) play an important role in the immunopathogenesis of MS, in part through the disruption of the BBB and the recruitment of inflammatory cells into the CNS. Moreover, MMPs can also enhance the cleavage of myelin basic protein (MBP) and the demyelination process. Regarding the growing data on the roles of MMPs and their tissue inhibitors (TIMPs) in the pathogenesis of MS, this review discusses the role of different types of MMPs, including MMP-2, -3, -7, -9, -12 and -25, in the immunopathogenesis and treatment of MS.

Keywords: Blood-Brain Barrier; Central Nervous System; Inflammation; Matrix Metalloproteinases; Multiple Sclerosis.

Figure 1:

In multiple sclerosis, matrix metalloproteinases (MMPs) are expressed in the central nervous system (CNS) by various cell types, including vascular endothelial cells, neuron, reactive astrocytes and the microglia, and accumulated inflammatory cells. In the CNS, the high numbers of MMPs lead to the perpetuation of neuroinflammation, which contributes to myelin degradation and axonal damage. BBB = blood-brain barrier; MBP = myelin basic protein; MAG = myelin-associated glycoprotein.