| First Author | Siddu A | Year | 2020 |
| Journal | Neurobiol Dis | Volume | 145 |
| Pages | 105042 | PubMed ID | 32798729 |
| Mgi Jnum | J:300567 | Mgi Id | MGI:6503569 |
| Doi | 10.1016/j.nbd.2020.105042 | Citation | Siddu A, et al. (2020) Beneficial effects of cysteamine in Thy1-alpha-Syn mice and induced pluripotent stem cells with a SNCA gene triplication. Neurobiol Dis 145:105042 |
| abstractText | A number of publications have reported that cysteamine has significant therapeutic effects on several aspects of Parkinson's disease (PD)-related pathology but none of these studies have evaluated its impact on pathological forms of alpha-Synuclein (alpha-Syn), one of the main hallmarks of PD. We therefore tested the efficacy of cysteamine on the Thy1-alpha-Syn mouse model which over-expresses full-length human wild-type alpha-Syn. Two-month (early stage disease) and 6-month old (late stage disease) mice and littermate controls were treated daily with cysteamine (20 mg/kg, i.p.) to assess the protective and restorative properties of this compound. After 6 weeks of treatment, animals were tested using a battery of motor tests. Cysteamine-treated transgenic mice displayed significant improvements in motor performance as compared to saline-treated transgenic littermates. Post-mortem readouts revealed a reduction in fibrillation, phosphorylation and total levels of overexpresed human alpha-Syn. To determine if such outcomes extended to human cells, the benefits of cysteamine were additionally tested using 6-hydroxydopamine (6-OHDA) treated neurons differentiated from induced pluripotent stem cells (iPSCs) derived from a PD patient harbouring a triplication of the SNCA gene. SNCA neurons treated with cysteamine exhibited significantly more intact/healthy neurites than cells treated with 6-OHDA alone. Additionally, SNCA neurons treated with cysteamine in the absence of 6-OHDA showed a trend towards lower total alpha-Syn levels. Overall, our in vivo and in vitro findings suggest that cysteamine can act as a disease-modifying molecule by enhancing -the survival of dopaminergic neurons and reducing pathological forms of alpha-Syn. |
