Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration

Gordon, Richard, Neal, Matthew L., Luo, Jie, Langley, Monica R., Harischandra, Dilshan S., Panicker, Nikhil, Charli, Adhithiya, Jin, Huajun, Anantharam, Vellareddy, Woodruff, Trent M., Zhou, Qun-Yong, Kanthasamy, Anumantha G. and Kanthasamy, Arthi (2016) Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration. Nature Communications, 7 12932.1-12932.18. doi:10.1038/ncomms12932


Author Gordon, Richard
Neal, Matthew L.
Luo, Jie
Langley, Monica R.
Harischandra, Dilshan S.
Panicker, Nikhil
Charli, Adhithiya
Jin, Huajun
Anantharam, Vellareddy
Woodruff, Trent M.
Zhou, Qun-Yong
Kanthasamy, Anumantha G.
Kanthasamy, Arthi
Title Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2016-10-05
Year available 2016
Sub-type Article (original research)
DOI 10.1038/ncomms12932
Open Access Status DOI
Volume 7
Start page 12932.1
End page 12932.18
Total pages 18
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Prokineticin-2 (PK2), a recently discovered secreted protein, regulates important physiological functions including olfactory biogenesis and circadian rhythms in the CNS. Interestingly, although PK2 expression is low in the nigral system, its receptors are constitutively expressed on nigrostriatal neurons. Herein, we demonstrate that PK2 expression is highly induced in nigral dopaminergic neurons during early stages of degeneration in multiple models of Parkinson’s disease (PD), including PK2 reporter mice and MitoPark mice. Functional studies demonstrate that PK2 promotes mitochondrial biogenesis and activates ERK and Akt survival signalling pathways, thereby driving neuroprotection. Importantly, PK2 overexpression is protective whereas PK2 receptor antagonism exacerbates dopaminergic degeneration in experimental PD. Furthermore, PK2 expression increased in surviving nigral dopaminergic neurons from PD brains, indicating that PK2 upregulation is clinically relevant to human PD. Collectively, our results identify a paradigm for compensatory neuroprotective PK2 signalling in nigral dopaminergic neurons that could have important therapeutic implications for PD.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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Created: Thu, 06 Oct 2016, 07:07:54 EST by Richard Gordon on behalf of School of Biomedical Sciences