The role of matrix metalloproteinase-9 in pro-inflammatory factors-induced brain inflammation and neurodegenerative diseases

Inflammation is a central pathogenic mechanism of various neuropathies including neurodegenerative diseases. In chronic neurodegenerative diseases such as Alzheimer's disease (AD) or Parkinson's disease (PD), the pathology is associated with an abnormal inflammatory response, characterized by the activation of several cell populations in the brain such as neuroglial cells. The relationships between inflammation and the development of these neuropathies involve complex molecular networks and processes. Recent evidence suggests that brain inflammation may impact on local inflammation in the brain diseases leading to over-production of several inflammatory mediators such as matrix metalloproteinases (MMPs), which may in turn influence functions including migration or apoptosis. Moreover, elevated levels of several pro-inflammatory factors including cytokines, peptides, pathogenic structures, per-oxidants in central nervous system (CNS) have been detected in the patients with brain disorders such as AD or PD. These pro-inflammatory factors exert as potent stimuli in brain inflammatory responses through up-regulation of diverse inflammatory mediators, in particular MMP-9. The expression of MMP-9 by these factors may be due to integration of the signaling networks that augment brain inflammation by recruiting immune cells and leading to neurodegenerative disorders. In this review, we discuss the mechanisms underlying the intracellular signaling pathways (e.g., calcium, protein kinase Cs, reactive oxygen species, or mitogen-activated protein kinases) involved in the expression of MMP-9 induced by pro-inflammatory factors in brain resident cells. Understanding of signaling transduction mechanisms involved in the expression of MMP-9 proteins and genes may provide helpful therapeutic managements for brain injury, inflammation, and neurodegenerative disorders.