| First Author | Matrone C | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 8 | Pages | e0160501 |
| PubMed ID | 27509067 | Mgi Jnum | J:254488 |
| Mgi Id | MGI:6099881 | Doi | 10.1371/journal.pone.0160501 |
| Citation | Matrone C, et al. (2016) Mannose 6-Phosphate Receptor Is Reduced in -Synuclein Overexpressing Models of Parkinsons Disease. PLoS One 11(8):e0160501 |
| abstractText | Increasing evidence points to defects in autophagy as a common denominator in most neurodegenerative conditions. Progressive functional decline in the autophagy-lysosomal pathway (ALP) occurs with age, and the consequent impairment in protein processing capacity has been associated with a higher risk of neurodegeneration. Defects in cathepsin D (CD) processing and alpha-synuclein degradation causing its accumulation in lysosomes are particularly relevant for the development of Parkinson's disease (PD). However, the mechanism by which alterations in CD maturation and alpha-synuclein degradation leads to autophagy defects in PD neurons is still uncertain. Here we demonstrate that MPR300 shuttling between endosomes and the trans Golgi network is altered in alpha-synuclein overexpressing neurons. Consequently, CD is not correctly trafficked to lysosomes and cannot be processed to generate its mature active form, leading to a reduced CD-mediated alpha-synuclein degradation and alpha-synuclein accumulation in neurons. MPR300 is downregulated in brain from alpha-synuclein overexpressing animal models and in PD patients with early diagnosis. These data indicate MPR300 as crucial player in the autophagy-lysosomal dysfunctions reported in PD and pinpoint MRP300 as a potential biomarker for PD. |
