English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

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 Ca 2+  signalling pathway. Analysis of the cells from idPD patients reveals a significant deficiency in store-operated PLA2g6-dependent Ca 2+  signalling, which we can mimic in a novel B6.Cg- Pla2g6   ΔEx2-VB   (PLA2g6 ex2 KO ) mouse model. Here we demonstrate that genetic or molecular impairment of PLA2g6-dependent Ca 2+  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.

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