| First Author | Kidana K | Year | 2018 |
| Journal | EMBO Mol Med | PubMed ID | 29311134 |
| Mgi Jnum | J:261970 | Mgi Id | MGI:6155302 |
| Doi | 10.15252/emmm.201708184 | Citation | Kidana K, et al. (2018) Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer's disease model mice. EMBO Mol Med |
| abstractText | Deposition of amyloid-beta (Abeta) as senile plaques is one of the pathological hallmarks in the brains of Alzheimer's disease (AD) patients. In addition, glial activation has been found in AD brains, although the precise pathological role of astrocytes remains unclear. Here, we identified kallikrein-related peptidase 7 (KLK7) as an astrocyte-derived Abeta degrading enzyme. Expression of KLK7 mRNA was significantly decreased in the brains of AD patients. Ablation of Klk7 exacerbated the thioflavin S-positive Abeta pathology in AD model mice. The expression of Klk7 was upregulated by Abeta treatment in the primary astrocyte, suggesting that Klk7 is homeostatically modulated by Abeta-induced responses. Finally, we found that the Food and Drug Administration-approved anti-dementia drug memantine can increase the expression of Klk7 and Abeta degradation activity specifically in the astrocytes. These data suggest that KLK7 is an important enzyme in the degradation and clearance of deposited Abeta species by astrocytes involved in the pathogenesis of AD. |
