GSE99559 SQSTM1/p62-directed metabolic reprogramming is required to prevent neurodegenerative disease

Contributors : Javier Calvo-Garrido ; Camilla Maffezzini ; Florian A Schober ; Paula Clemente ; Elias Uhlin ; Malin Kele ; Henrik Stranneheim ; Nicole Lesko ; Helene Bruhn ; Per Svenningsson ; Anna Falk ; Anna Wedell ; Christoph Freyer ; Anna WredenbergSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensNeurodegenerative disorders are an increasingly common and irreversible burden on society, often affecting the ageing population, but their aetiology and disease mechanisms are poorly understood. Studying monogenic neurodegenerative diseases, with known genetic cause, provides an opportunity to understand cellular mechanisms also affected in more complex disorders. We recently reported that loss-of-function mutations in the autophagy adaptor protein, SQSTM1/p62, lead to a slowly progressive neurodegenerative disease presenting in childhood. To further elucidate the neuronal involvement, we studied the cellular consequences of loss of p62 in a neuroepithelial stem cell model and differentiated neurones. Transcriptomic and proteomic analyses show that p62 is essential for neuronal differentiation by controlling the metabolic shift from aerobic glycolysis to oxidative phosphorylation required for neuronal maturation. This shift is mediated by the failure of regulating lactate dehydrogenase and hexokinase 2 expression due to the loss of p62. The findings demonstrate an important role for p62 in neuronal energy metabolism and a direct...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research