| First Author | Yan DY | Year | 2019 |
| Journal | Neurotox Res | Volume | 36 |
| Issue | 1 | Pages | 66-80 |
| PubMed ID | 30796692 | Mgi Jnum | J:295558 |
| Mgi Id | MGI:6453963 | Doi | 10.1007/s12640-019-00016-y |
| Citation | Yan DY, et al. (2019) Mn-Induced Neurocytes Injury and Autophagy Dysfunction in Alpha-Synuclein Wild-Type and Knock-Out Mice: Highlighting the Role of Alpha-Synuclein. Neurotox Res 36(1):66-80 |
| abstractText | Overexposure to manganese (Mn) is an important environmental risk factor for Parkinsonian-like symptoms referred to as manganism. Alpha-synuclein (alpha-Syn) oligomerization is a major cause in Mn-induced neurotoxicity. Autophagy, as an adjust response to control intracellular protein homeostasis, is involved in the degradation of alpha-Syn monomers or oligomers. Furthermore, autophagy dysregulation is also related to development of neurodegenerative disorders. Hence, we speculated that there was an interaction effect between alpha-Syn oligomerization and autophagy upon Mn exposure. In this study, we applied alpha-Syn gene knockout mice (alpha-Syn(-/-)) and wild-type mice (alpha-Syn(+/+)) treated with three different concentrations of MnCl2 (50, 100, and 200 mumol/kg) to elucidate the physiological role of alpha-Syn in Mn-induced autophagy dysregulation and neurocytes injury. We found that activation of chaperone-mediated autophagy (CMA) pathway by Mn was independent of alpha-Syn. Additionally, alpha-Syn could ameliorate excessive autophagy induced by high dose Mn (200 mumol/kg). Next, we used 5 mg/kg Rapamycin (Rap) or 3-methyladenine (3-MA) to regulate autophagy. The study revealed that autophagy is involved in Mn-induced alpha-Syn oligomerization and neurocytes injury. Taken together, these findings indicated that alpha-Syn oligomerization might be the major responsible for the Mn-induced autophagy dysregulation and neurocytes injury. |
