Mutations in the gene PLA2G6 cause neurodegeneration by a yet undefined mechanism.
In this study we analyzed the Golgi and glycosylation in cultured skin fibroblasts in three patients with PLA2G6-associated neurodegeneration (PLAN). Although each patient had different mutations, all had altered Golgi morphology and protein O-linked glycosylation that were rescued by overexpression of wild type PLA2G6.
The Golgi and glycosylation are essential for correct processing and distribution of proteins. Defects in either may lead to Lewy body and Tau pathology, two neuropathological features of PLAN. Disruption of the Golgi and glycosylation may, therefore, cause the pathogenesis of PLAN and perhaps other neurodegenerative disorders. (By Dr. Mariska Davids, http://jmg.bmj.com/content/early/2015/12/14/jmedgenet-2015-103338 )
