Other
18 Authors
- Arancio O,
- Vangavaragu JR,
- McKhann GM,
- Chen JX,
- Glaser E,
- Yan SS,
- Wang Y,
- Sosunov AA,
- Zhang Z,
- Fang D,
- Zhong C,
- Sun Q,
- Du H,
- Guo L,
- Yan S,
- Wu L,
- Hu G,
- Rabinowitz M
| First Author | Fang D | Year | 2015 |
| Journal | Hum Mol Genet | Volume | 24 |
| Issue | 18 | Pages | 5198-210 |
| PubMed ID | 26123488 | Mgi Jnum | J:225842 |
| Mgi Id | MGI:5694555 | Doi | 10.1093/hmg/ddv241 |
| Citation | Fang D, et al. (2015) Increased neuronal PreP activity reduces Abeta accumulation, attenuates neuroinflammation and improves mitochondrial and synaptic function in Alzheimer disease's mouse model. Hum Mol Genet 24(18):5198-210 |
| abstractText | Accumulation of amyloid-beta (Abeta) in synaptic mitochondria is associated with mitochondrial and synaptic injury. The underlying mechanisms and strategies to eliminate Abeta and rescue mitochondrial and synaptic defects remain elusive. Presequence protease (PreP), a mitochondrial peptidasome, is a novel mitochondrial Abeta degrading enzyme. Here, we demonstrate for the first time that increased expression of active human PreP in cortical neurons attenuates Alzheimer disease's (AD)-like mitochondrial amyloid pathology and synaptic mitochondrial dysfunction, and suppresses mitochondrial oxidative stress. Notably, PreP-overexpressed AD mice show significant reduction in the production of proinflammatory mediators. Accordingly, increased neuronal PreP expression improves learning and memory and synaptic function in vivo AD mice, and alleviates Abeta-mediated reduction of long-term potentiation (LTP). Our results provide in vivo evidence that PreP may play an important role in maintaining mitochondrial integrity and function by clearance and degradation of mitochondrial Abeta along with the improvement in synaptic and behavioral function in AD mouse model. Thus, enhancing PreP activity/expression may be a new therapeutic avenue for treatment of AD. |
