| First Author | Fragkouli A | Year | 2014 |
| Journal | Neurobiol Dis | Volume | 70 |
| Pages | 179-89 | PubMed ID | 25008761 |
| Mgi Jnum | J:215635 | Mgi Id | MGI:5605933 |
| Doi | 10.1016/j.nbd.2014.06.021 | Citation | Fragkouli A, et al. (2014) Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer's 5xFAD mice. Neurobiol Dis 70:179-89 |
| abstractText | Accumulation of amyloid-beta (Alphabeta) peptide is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Lowering Abeta levels in the brain may thus improve synaptic and cognitive deficits observed in AD patients. In the non-amyloidogenic pathway, the amyloid-beta precursor protein (APP) is cleaved within the Abeta peptide sequence by alpha-secretases, giving rise to the potent neurotrophic N-terminal fragment sAlphaPPalpha. We have previously reported that gelatinase B/matrix metalloproteinase 9 (MMP-9), a matrix metalloproteinase critically involved in neuronal plasticity, acts as alpha-secretase both in vitro and in vivo and reduces Abeta levels in vitro. In the present study, we demonstrate that neuronal overexpression of MMP-9 in a transgenic AD mouse model harboring five familial AD-related mutations (5xFAD) resulted in increased sAPPalpha levels and decreased Abeta oligomers without affecting amyloid plaque load in the brain. Functionally, overexpression of MMP-9 prevented the cognitive deficits displayed by 5xFAD mice, an improvement that was accompanied by increased levels of the pre-synaptic protein synaptophysin and mature brain-derived neurotrophic factor (BDNF) in the brain. These results suggest that in vivo activation of endogenous MMP-9 could be a promising target for interference with development and/or progression of AD. |
