- Integration of CiNii Books functions for fiscal year 2025 has completed
- Trial version of CiNii Research Knowledge Graph Search feature is available on CiNii Labs
- 【Updated on November 26, 2025】Regarding the recording of “Research Data” and “Evidence Data”
- Start the collection of all publicly IRDB content
- Incorporate Research Data from KAKEN
Apoptosis signal-regulating kinase 1 modulates the phenotype of α-synuclein transgenic mice
Bibliographic Information
- Published
- 2015-01
- Resource Type
- journal article
- Rights Information
-
- https://www.elsevier.com/tdm/userlicense/1.0/
- DOI
-
- 10.1016/j.neurobiolaging.2014.07.034
- Publisher
- Elsevier BV
Search this article
Description
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.
Journal
-
- Neurobiology of Aging
-
Neurobiology of Aging 36 (1), 519-526, 2015-01
Elsevier BV
