Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

Figure 3

Schematic representation of the involvement of MMPs in Alzheimer’s disease pathology. Aβ peptides produced from APP processing form oligomers that subsequently form amyloid deposits or plaques in the brain parenchyma. Aβ oligomers activate inflammatory cells in the brain (astrocytes, microglia, and choroid plexus epithelium). Once activated, microglia change their shape, migrate close to plaques, and begin to secrete proinflammatory cytokines and MMPs. Secreted MMPs degrade Aβ and, on the other hand, exacerbate inflammation in the brain, leading to death of neurons. These cytokines and MMPs also affect the endothelial tight junctions, alter the pericyte phenotypes, and contribute to increased BBB permeability. Similarly, oligomers in the CSF activate the choroid plexus epithelium, which leads to the release of proinflammatory cytokines and MMPs. These secreted MMPs further damage the tight junctions at the BCSFB. Aβ, β-amyloid; BBB, blood-brain barrier; BCSFB, blood-cerebrospinal fluid barrier; CSF, cerebrospinal fluid; MMP, matrix metalloproteinase; TJs, tight junctions.