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 researchers focused on the poorly understood PARK14 disease locus (Pla2g6gene) 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 authors can mimic in a novel mouse model.
They 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 the ability to mimic this pathology in a novel genetic mouse model opens new opportunities for finding a cure for this devastating neurodegenerative disease.