A pivotal role of matrix metalloproteinase‐3 activity in dopaminergic neuronal degeneration via microglial activation

• DOI: 10.1096/fj.06-5865com
• Publication Date: 2006-11-21T01:48:55Z
• Authors: Yoon Seong Kim; Dong Hee Choi; Michelle L. Block; Stefan Lorenzl; Lichuan Yang; Youn Jung Kim; Shuei Sugama; Byung Pil Cho; Onyou Hwang; Susan E. Browne; Soo Yul Kim; Jau‐Shyong Hong; M. Flint Beal; Tong H. Joh
• Keywords: MPTP

Recent studies have demonstrated that activated microglia play an important role in dopamine (DA) neuronal degeneration Parkinson disease (PD) by generating NADPH-oxidase (NADPHO)-derived superoxide. However, the molecular mechanisms underlie microglial activation DA cell death are still disputed. We report here matrix metalloproteinase-3 (MMP-3) was newly induced and stressed cells, active form of MMP-3 (actMMP-3) released into medium. The actMMP-3, as well catalytically recombinant (cMMP-3) led to superoxide generation enhanced death. cMMP-3 caused mesencephalic neuron-glia mixed culture wild-type (WT) mice, but this attenuated NADPHO subunit null mice (gp91(phox-/-)), suggesting mediated cMMP-3-induced production Furthermore, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected animal model PD, nigrostriatal degeneration, activation, were largely MMP-3-/- mice. These results indicate actMMP-3 from neurons is responsible for NADPHO-derived eventually enhances degeneration. Our could lead a novel therapeutic approach PD.