| First Author | Lee KW | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 1 | Pages | 519-26 |
| PubMed ID | 25219466 | Mgi Jnum | J:218432 |
| Mgi Id | MGI:5617456 | Doi | 10.1016/j.neurobiolaging.2014.07.034 |
| Citation | Lee KW, et al. (2015) Apoptosis signal-regulating kinase 1 modulates the phenotype of alpha-synuclein transgenic mice. Neurobiol Aging 36(1):519-26 |
| abstractText | alpha-Synuclein is a key pathogenic protein in alpha-synucleinopathies including Parkinson's disease, and its overexpression and aggregation in model systems are associated with a neuroinflammatory response and increased oxidative stress. Apoptosis signal-regulating kinase 1 (ASK1) is activated upon stress signaling events such as oxidative stress and is a central player linking oxidative stress with neuroinflammation. Here, we demonstrate that overexpression of human alpha-synuclein activates ASK1 in both PC12 cells and in the brains of alpha-synuclein transgenic mice. Deleting ASK1 in mice mitigates the neuronal damage and neuroinflammation induced by alpha-synuclein and improves performance of the animals on the rotarod. ASK1 deletion does not impact the aggregation profile or phosphorylation state of alpha-synuclein in the mouse brain. These results collectively implicate ASK1 in the cascade of events triggered by alpha-synuclein overexpression, likely because of the inflammatory response and oxidative stress that lead to ASK1 activation. These conclusions raise the possibility that potent antioxidants and anti-inflammatory agents may ameliorate the phenotype of alpha-synucleinopathies. |
