Document Type

Article

Publication Date

9-22-2017

Comments

This article has been peer reviewed. It is the author’s final published version in Scientific Reports

Volume 7, Issue 1, December 2017, Article number 12178.

The published version is available at DOI: 10.1038/s41598-017-12379-3. Copyright © Yoon et al.

Abstract

Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1(-/-) mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP(+))-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP(+)-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP(+)-induced neurotoxicity by blocking ASK1-mediated signaling.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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