| First Author | Du H | Year | 2011 |
| Journal | Neurobiol Aging | Volume | 32 |
| Issue | 3 | Pages | 398-406 |
| PubMed ID | 19362755 | Mgi Jnum | J:173741 |
| Mgi Id | MGI:5050070 | Doi | 10.1016/j.neurobiolaging.2009.03.003 |
| Citation | Du H, et al. (2011) Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging 32(3):398-406 |
| abstractText | Mitochondrial stress is one of the early features of Alzheimer disease (AD). Mitochondrial Abeta has been linked to mitochondrial toxicity. Our recent study demonstrated that cyclophilin D (CypD) mediated mitochondrial permeability transition pore (mPTP) is an important mechanism for neuronal and synaptic stress induced by both Abeta and oxidative stress. In transgenic AD-type mice overexpressing mutant amyloid precursor protein (APP) and Abeta (mAPP), CypD deficiency improves mitochondrial and synaptic function and learning/memory up to 12 months old. Here we provide evidence of the protective effects of CypD deficiency in aged AD mice (22-24 months). Cyp D deficient mAPP mice demonstrate less calcium-induced mitochondrial swelling, increased mitochondrial calcium uptake capacity, preserved mitochondrial respiratory function and improved spatial learning/memory even in old age (known to be the age for late stage AD pathology and synaptic dysfunction). These data demonstrate that abrogation of CypD results in persistent life-long protection against Abeta toxicity in an Alzheimer's disease mouse model, thereby suggesting that blockade of CypD may be of benefit for Alzheimer disease treatment. |
