| First Author | Baksi S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 12843 |
| PubMed ID | 28993630 | Mgi Jnum | J:323747 |
| Mgi Id | MGI:6835438 | Doi | 10.1038/s41598-017-12862-x |
| Citation | Baksi S, et al. (2017) alpha-Synuclein impairs ferritinophagy in the retinal pigment epithelium: Implications for retinal iron dyshomeostasis in Parkinson's disease. Sci Rep 7(1):12843 |
| abstractText | Retinal degeneration is prominent in Parkinson's disease (PD), a neuromotor disorder associated with aggregation of alpha-synuclein (alpha-syn) in the substantia-nigra (SN). Although alpha-syn is expressed in the neuroretina, absence of prominent aggregates suggests altered function as the likely cause of retinal pathology. We demonstrate that alpha-syn impairs ferritinophagy, resulting in the accumulation of iron-rich ferritin in the outer retina in-vivo and retinal-pigment-epithelial (RPE) cells in-vitro. Over-expression of Rab1a restores ferritinophagy, suggesting that alpha-syn impairs lysosomal function by disrupting the trafficking of lysosomal hydrolases. Surprisingly, upregulation of ferritin in RPE cells by exogenous iron in-vitro stimulated the release of ferritin and alpha-syn in exosomes, suggesting that iron overload due to impaired ferritinophagy or other cause(s) is likely to initiate prion-like spread of alpha-syn and ferritin, creating retinal iron dyshomeostasis and associated cytotoxicity. Since over-expression of alpha-syn is a known cause of PD, these results explain the likely cause of PD-associated retinal degeneration. |
