Bioenergetic and proteolytic defects in fibroblasts from patients with sporadic Parkinson's disease

摘要: Abstract Background Parkinson's disease (PD) is a complex and the current interest focus of scientific research both investigating variety causes that underlie PD pathogenesis, identifying reliable biomarkers to diagnose monitor progression pathology. Investigation on pathogenic mechanisms in peripheral cells, such as fibroblasts derived from patients with sporadic age/gender matched controls, might generate deeper understanding deficits affecting dopaminergic neurons and, possibly, new tools applicable clinical practice. Methods Primary fibroblast cultures were established skin biopsies. Increased susceptibility PD-related toxin rotenone was determined apoptosis- necrosis-specific cell death assays. Protein quality control evaluated assessing efficiency Ubiquitin Proteasome System (UPS) protein levels autophagic markers. Changes cellular bioenergetics monitored by measuring oxygen consumption glycolysis-dependent medium acidification. The oxido-reductive status detecting mitochondrial superoxide production oxidation proteins lipids. Results showed higher vulnerability necrotic induced I inhibitor rotenone, reduced UPS function decreased maximal rotenone-sensitive respiration. No changes autophagy redox markers detected. Conclusions Our study shows increased presence proteolytic bioenergetic typically sustain neurodegenerative process can be detected idiopathic patients. Fibroblasts therefore represent powerful minimally invasive tool investigate mechanisms, which translate into considerable advances management disease.