| First Author | Suzuki Y | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 3 | Pages | 790-9 |
| PubMed ID | 24405769 | Mgi Jnum | J:206463 |
| Mgi Id | MGI:5550315 | Doi | 10.1016/j.ajpath.2013.11.018 |
| Citation | Suzuki Y, et al. (2014) Cystatin C triggers neuronal degeneration in a model of multiple system atrophy. Am J Pathol 184(3):790-9 |
| abstractText | Multiple system atrophy is an intractable neurodegenerative disease caused by alpha-synuclein (alpha-syn) accumulation in oligodendrocytes and neurons. With the use of a transgenic mouse model overexpressing human alpha-syn in oligodendrocytes, we demonstrated that oligodendrocytic alpha-syn inclusions induce neuronal alpha-syn accumulation, resulting in progressive neuronal degeneration. The mechanism through which oligodendrocytic alpha-syn inclusions trigger neuronal alpha-syn accumulation leading to multiple system atrophy is unknown. In this study, we identified cystatin C, an oligodendrocyte-derived secretory protein that triggers alpha-syn up-regulation and insoluble alpha-syn accumulation, in neurons of the mouse central nervous system. Cystatin C was released by mouse oligodendrocytes overexpressing human alpha-syn, and extracellular cystatin C increased the expression of the endogenous alpha-syn gene in wild-type mouse neurons. These neurons then accumulate insoluble alpha-syn and may undergo apoptosis. Cystatin C is a potential pathogenic signal triggering neurodegeneration in multiple system atrophy. |
