Details

Autor(en) / Beteiligte

• Lee, Kang-Woo
• Woo, Jong-Min
• Im, Joo-Young
• Park, Eun S
• He, Liqiang
• Ichijo, Hidenori
• Junn, Eunsung
• Mouradian, M. Maral

Titel

Apoptosis signal-regulating kinase 1 modulates the phenotype of α-synuclein transgenic mice

Ist Teil von

• Neurobiology of aging, 2015-01, Vol.36 (1), p.519-526

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract α-Synuclein is a key pathogenic protein in α-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 α-synuclein activates ASK1 in both PC12 cells and in the brains of α-synuclein transgenic mice. Deleting ASK1 in mice mitigates the neuronal damage and neuroinflammation induced by α-synuclein and improves performance of the animals on the rotarod. ASK1 deletion does not impact the aggregation profile or phosphorylation state of α-synuclein in the mouse brain. These results collectively implicate ASK1 in the cascade of events triggered by α-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 α-synucleinopathies.