| First Author | Spencer B | Year | 2013 |
| Journal | Mol Ther | Volume | 21 |
| Issue | 1 | Pages | 31-41 |
| PubMed ID | 22508489 | Mgi Jnum | J:315246 |
| Mgi Id | MGI:6829894 | Doi | 10.1038/mt.2012.66 |
| Citation | Spencer B, et al. (2013) Lentivirus mediated delivery of neurosin promotes clearance of wild-type alpha-synuclein and reduces the pathology in an alpha-synuclein model of LBD. Mol Ther 21(1):31-41 |
| abstractText | Neurosin is a predominant serine protease in the central nervous system (CNS) and has been shown to play a role in the clearance of alpha-synuclein (alpha-syn) which is centrally involved in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although it has been previously shown that neurosin and alpha-syn colocalize and that neurosin degrades alpha-syn aggregates in vitro, it is not clear if neurosin is dysregulated in the brains of patients with PD/DLB and to what extent delivery of neurosin into the CNS might ameliorate the deficits associated with alpha-syn accumulation in vivo. We analyzed the levels of neurosin in the brains of patients with PD/DLB and in alpha-syn transgenic (tg) models. With increased accumulation of alpha-syn, we observed decreased neurosin expression. Lentiviral vector (LV) driven expression of neurosin in neuronal cell cultures reduced the accumulation of wild type but not A53T alpha-syn and prevented alpha-syn associated toxicity. Neuropathological analysis following delivery of LV-Neurosin to alpha-syn tg mice resulted in reduced accumulation of alpha-syn and reversal of neurodegenerative alterations in wild type but not A53T alpha-syn tg mice. Therefore, viral vector driven expression of neurosin may warrant further investigation as a potential therapeutic tool for DLB. |
