| First Author | Meng L | Year | 2022 |
| Journal | Aging Cell | Volume | 21 |
| Issue | 5 | Pages | e13619 |
| PubMed ID | 35443102 | Mgi Jnum | J:355367 |
| Mgi Id | MGI:7282352 | Doi | 10.1111/acel.13619 |
| Citation | Meng L, et al. (2022) A synapsin cleavage fragment contributes to synaptic dysfunction in Alzheimer's disease. Aging Cell 21(5):e13619 |
| abstractText | Synaptic dysfunction is a key feature of Alzheimer's disease (AD). However, the molecular mechanisms underlying synaptic dysfunction remain unclear. Here, we show that synapsin , one of the most important synaptic proteins, is fragmented by the cysteine proteinase asparagine endopeptidase (AEP). AEP cleaves synapsin at N82 in the brains of AD patients and generates the C-terminal synapsin (83-705) fragment. This fragment is abnormally distributed in neurons and induces synaptic dysfunction. Overexpression of AEP in the hippocampus of wild-type mice results in the production of the synapsin (83-705) fragment and induces synaptic dysfunction and cognitive deficits. Moreover, overexpression of the AEP-generated synapsin (83-705) fragment in the hippocampus of tau P301S transgenic mice and wild-type mice promotes synaptic dysfunction and cognitive deficits. These findings suggest a novel mechanism of synaptic dysfunction in AD. |
