Reference - Detail
| RRC ID | 52562 |
|---|---|
| Author | Kidana K, Tatebe T, Ito K, Hara N, Kakita A, Saito T, Takatori S, Ouchi Y, Ikeuchi T, Makino M, Saido TC, Akishita M, Iwatsubo T, Hori Y, Tomita T. |
| Title | Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer's disease model mice. |
| Journal | EMBO Mol Med |
| Abstract |
Deposition of amyloid-β (Aβ) 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 Aβ degrading enzyme. Expression of KLK7 mRNA was significantly decreased in the brains of AD patients. Ablation of Klk7 exacerbated the thioflavin S-positive Aβ pathology in AD model mice. The expression of Klk7 was upregulated by Aβ treatment in the primary astrocyte, suggesting that Klk7 is homeostatically modulated by Aβ-induced responses. Finally, we found that the Food and Drug Administration-approved anti-dementia drug memantine can increase the expression of Klk7 and Aβ degradation activity specifically in the astrocytes. These data suggest that KLK7 is an important enzyme in the degradation and clearance of deposited Aβ species by astrocytes involved in the pathogenesis of AD. |
| Volume | 10(3) |
| Published | 2018-3-1 |
| DOI | 10.15252/emmm.201708184 |
| PII | emmm.201708184 |
| PMID | 29311134 |
| PMC | PMC5840542 |
| MeSH | Alzheimer Disease / metabolism* Alzheimer Disease / pathology* Amyloid / metabolism* Amyloid beta-Peptides / metabolism Animals Astrocytes / drug effects Astrocytes / metabolism Brain / metabolism Brain / pathology Cell Line, Tumor Culture Media, Conditioned / pharmacology Disease Models, Animal Humans Kallikreins / deficiency* Kallikreins / genetics Kallikreins / metabolism Memantine / pharmacology Mice, Knockout Proteolysis / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Up-Regulation / drug effects |
| IF | 8.821 |
| Times Cited | 7 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MG6(RCB2403) |