| First Author | Pajoohesh-Ganji A | Year | 2014 |
| Journal | Brain Res | Volume | 1560 |
| Pages | 73-82 | PubMed ID | 24630972 |
| Mgi Jnum | J:216265 | Mgi Id | MGI:5608572 |
| Doi | 10.1016/j.brainres.2014.02.049 | Citation | Pajoohesh-Ganji A, et al. (2014) Inhibition of amyloid precursor protein secretases reduces recovery after spinal cord injury. Brain Res 1560:73-82 |
| abstractText | Amyloid-beta (Abeta) is produced through the enzymatic cleavage of amyloid precursor protein (APP) by beta (Bace1) and gamma-secretases. The accumulation and aggregation of Abeta as amyloid plaques is the hallmark pathology of Alzheimers disease and has been found in other neurological disorders, such as traumatic brain injury and multiple sclerosis. Although the role of Abeta after injury is not well understood, several studies have reported a negative correlation between Abeta formation and functional outcome. In this study we show that levels of APP, the enzymes cleaving APP (Bace1 and gamma-secretase), and Abeta are significantly increased from 1 to 3 days after impact spinal cord injury (SCI) in mice. To determine the role of Abeta after SCI, we reduced or inhibited Abeta in vivo through pharmacological (using DAPT) or genetic (Bace1 knockout mice) approaches. We found that these interventions significantly impaired functional recovery as evaluated by white matter sparing and behavioral testing. These data are consistent with a beneficial role for Abeta after SCI. |
