Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson’s disease
Fiona Dick,
Ole-Bjørn Tysnes,
Guido W. Alves,
Gonzalo S. Nido,
Charalampos Tzoulis
Affiliations
Fiona Dick
Neuro-SysMed Center of Excellence for Clinical Research in Neurological Diseases Department of Neurology, Haukeland University Hospital Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway; K.G Jebsen Center for Translational Research in Parkinson’s disease, University of Bergen, Bergen, Norway
Ole-Bjørn Tysnes
Neuro-SysMed Center of Excellence for Clinical Research in Neurological Diseases Department of Neurology, Haukeland University Hospital Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway
Guido W. Alves
The Norwegian Center for Movement Disorders and Department of Neurology, Stavanger University Hospital, Stavanger, Norway; Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway
Gonzalo S. Nido
Neuro-SysMed Center of Excellence for Clinical Research in Neurological Diseases Department of Neurology, Haukeland University Hospital Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway; K.G Jebsen Center for Translational Research in Parkinson’s disease, University of Bergen, Bergen, Norway
Charalampos Tzoulis
Neuro-SysMed Center of Excellence for Clinical Research in Neurological Diseases Department of Neurology, Haukeland University Hospital Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway; K.G Jebsen Center for Translational Research in Parkinson’s disease, University of Bergen, Bergen, Norway; Corresponding author
Summary: Aberrant proteostasis is thought to be implicated in Parkinson’s disease (PD), but patient-derived evidence is scant. We hypothesized that impaired proteostasis is reflected as altered transcriptome-proteome correlation in the PD brain. We integrated transcriptomic and proteomic data from prefrontal cortex of PD patients and young and aged controls to assess RNA-protein correlations across samples. The aged brain showed a genome-wide decrease in mRNA-protein correlation. Genes encoding synaptic vesicle proteins showed negative correlations, likely reflecting spatial separation of mRNA and protein into soma and synapses. PD showed a broader transcriptome-proteome decoupling, consistent with a proteome-wide decline in proteostasis. Genes showing negative correlation in PD were enriched for proteasome subunits, indicating accentuated spatial separation of transcript and protein in PD neurons. In addition, PD showed positive correlations for mitochondrial respiratory chain genes, suggesting a tighter regulation in the face of mitochondrial dysfunction. Our results support the hypothesis that aberrant proteasomal function is implicated in PD pathogenesis.
