Role of matrix metalloproteinase‐3 in neurodegeneration

다국어 초록 (Multilingual Abstract)

<P> <I>J. Neurochem.</I> (2011) <B>116,</B> 22–32.</P><P><B>Abstract</B></P><P>Matrix metalloproteinase‐3 (MMP‐3) is a member of the class of zinc‐dependent proteases known to degrade the extracellular matrix. MMP‐3 activity is regulated at three different levels: gene expression, proteolytic activation of the zymogen, and inhibition by the endogenous tissue inhibitors of metalloproteinase. A line of evidence indicates a role of MMP‐3 in neurodegeneration. In neuronal cells, MMP‐3 expression is increased in response to cell stress, and the cleaved, active MMP‐3 participates in apoptotic signaling. In the extracellular space, MMP‐3 triggers microglia to produce proinflammatory and cytotoxic molecules as well as MMP‐3, which in turn contribute to neuronal damage. MMP‐3 is increased in various experimental models of Parkinson’s disease that are produced by selective toxins and by inflammagen, and the neuronal death is attenuated by various ways that inhibit MMP‐3. α‐Synuclein, whose gene mutations are associated with familial forms of Parkinson’s disease, is proteolyzed by MMP‐3. Contribution of MMP‐3 toward the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases has also been suggested. Thus, modulation of MMP‐3 expression and/or activity could be of therapeutic value for neurodegenerative diseases.</P>