Impairment of PARK14-dependent Ca2+ signalling is a novel determinant of Parkinson’s disease

Qingde Zhou, Allen Yen, Grzegorz Rymarczyk, Hirohide Asai, Chelsea Trengrove, Nadine Aziz, Michael T. Kirber, Gustavo Mostoslavsky, Tsuneya Ikezu, Benjamin Wolozin and Victoria M. Bolotina ()
Additional contact information
Qingde Zhou: Boston University School of Medicine
Allen Yen: Boston University School of Medicine
Grzegorz Rymarczyk: Boston University School of Medicine
Hirohide Asai: Boston University School of Medicine
Chelsea Trengrove: Boston University School of Medicine
Nadine Aziz: Boston University School of Medicine
Michael T. Kirber: Boston University School of Medicine
Gustavo Mostoslavsky: Center for Regenerative Medicine, Boston University School of Medicine
Tsuneya Ikezu: Boston University School of Medicine
Benjamin Wolozin: Boston University School of Medicine
Victoria M. Bolotina: Boston University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract The etiology of idiopathic Parkinson’s disease (idPD) remains enigmatic despite recent successes in identification of genes (PARKs) that underlie familial PD. To find new keys to this incurable neurodegenerative disorder we focused on the poorly understood PARK14 disease locus (Pla2g6 gene) and the store-operated Ca2+ signalling pathway. Analysis of the cells from idPD patients reveals a significant deficiency in store-operated PLA2g6-dependent Ca2+ signalling, which we can mimic in a novel B6.Cg-Pla2g6ΔEx2-VB (PLA2g6 ex2KO) mouse model. Here we demonstrate that genetic or molecular impairment of PLA2g6-dependent Ca2+ signalling is a trigger for autophagic dysfunction, progressive loss of dopaminergic (DA) neurons in substantia nigra pars compacta and age-dependent L-DOPA-sensitive motor dysfunction. Discovery of this previously unknown sequence of pathological events, its association with idPD and our ability to mimic this pathology in a novel genetic mouse model opens new opportunities for finding a cure for this devastating neurodegenerative disease.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10332 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10332

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10332

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().